The impact of carotid plaque screening on motivation for smoking cessation.

Showing smokers their own atherosclerotic plaques might increase motivation for smoking cessation, since they underestimate their own risk for smoking-related diseases. To assess the feasibility and optimal processes of studying the impact of carotid atherosclerotic plaque screening in smokers, we enrolled 30 daily cigarette smokers, aged 40-70 years, in an observational pre-post pilot study. All smokers underwent smoking cessation counseling, nicotine replacement therapy, a carotid ultrasound, an educational tutorial on atherosclerosis, baseline and 2-month motivation to change assessment, and assessment of smoking cessation at 2 months. Participants had a mean smoking duration of 34 years (SD = 7). Carotid plaques were present in 22 smokers (73%). Between baseline and 2 months after plaque screening, motivation for smoking cessation increased from 7.4 to 8.4 out of 10 (p = .02), particularly in those with plaques (7.2 to 8.7, p = .008). At 2 months, the smoking quit rate was 63%, with a quit rate of 73% in those with plaques vs. 38% in those without plaques (p = .10). Perceived stress, anxiety, and depression did not increase after screening. 96% of respondents answered correctly at least 80% of questions regarding atherosclerosis knowledge at baseline and after 2 months. In conclusion, studying the process of screening for carotid plaques for the purpose of increasing motivation for smoking cessation, in addition to counseling and drug therapy for smoking cessation in long-term smokers, appears feasible. The impact of carotid plaque screening on smoking cessation should be examined in larger randomized controlled trials with sufficient power to assess the impact on long-term smoking cessation rates.

Colonoscopy is the preferred colorectal cancer screening method in a population-based program.

BACKGROUND AND STUDY AIMS: Various screening methods for colorectal cancer (CRC) are promoted by professional societies; however, few data are available about the factors that determine patient participation in screening, which is crucial to the success of population-based programs. This study aimed (i) to identify factors that determine acceptance of screening and preference of screening method, and (ii) to evaluate procedure success, detection of colorectal neoplasia, and patient satisfaction with screening colonoscopy. PATIENTS AND METHODS: Following a public awareness campaign, the population aged 50 - 80 years was offered CRC screening in the form of annual fecal occult blood tests, flexible sigmoidoscopy, a combination of both, or colonoscopy. RESULTS: 2731 asymptomatic persons (12.0 % of the target population) registered with and were eligible to take part in the screening program. Access to information and a positive attitude to screening were major determinants of participation. Colonoscopy was the method preferred by 74.8 % of participants. Advanced colorectal neoplasia was present in 8.5 %; its prevalence was higher in males and increased with age. Significant complications occurred in 0.5 % of those undergoing colonoscopy and were associated with polypectomy or sedation. Most patients were satisfied with colonoscopy and over 90 % would choose it again for CRC screening. CONCLUSIONS: In this population-based study, only a small proportion of the target population underwent CRC screening despite an extensive information campaign. Colonoscopy was the preferred method and was safe. The determinants of participation in screening and preference of screening method, together with the distribution of colorectal neoplasia in different demographic categories, provide a rationale for improving screening procedures.

The 'help' question doesn't help when screening for major depression : external validation of the three-question screening test for primary care patients managed for physical complaints

La dépression majeure est fréquente chez les patients qui consultent un cabinet de médecine générale. Elle reste toutefois difficile à diagnostiquer car elle est souvent masquée par une ou plusieurs plaintes physiques qui sont l'unique motif de consultation. Pour aider le médecin généraliste à démasquer ce trouble, un test de dépistage composé de deux questions a été développé et validé. Ce test indique une probabilité accrue de dépression si le patient répond positivement à au moins une des deux questions suivantes : « Est-ce que, durant le mois qui a précédé, vous vous êtes senti(e) triste, déprimé(e), désespéré(e) ? » et « Durant le mois qui a précédé, avez-vous ressenti un manque d'intérêt et de plaisir dans la plupart des activités que d'habitude vous appréciez ? ». Une troisième question, ajoutée aux deux questions ci-dessus, a été proposée récemment afin d'améliorer les performances de ce test de dépistage. Cette troisième question rend le test négatif si le patient répond négativement à la question suivante : « Souhaitez-vous de l'aide pour cela ? ». Une étude avait indiqué que l'ajout de la question supplémentaire améliorait la spécificité du test sans réduire sa sensibilité. Objectifs Il s'agissait de décrire la performance de deux tests de dépistage de la dépression majeure, composés, respectivement, de deux et de trois questions, dans une population de patients consultant dans un cabinet de médecine générale pour une plainte physique, et de les valider. Méthode Les réponses aux questions des tests de dépistage de la dépression dans la population de la cohorte SODA (Somatisation, Depression, Anxiety) ont été utilisées. Il s'agissait de patients de plus de 18 ans, sélectionnés aléatoirement, consultant pour au moins une plainte physique auprès de 24 médecins généralistes de Suisse Romande, réexaminés une année après l'inclusion dans la cohorte. Le questionnaire validé « Full Patient Health Questionnaire » a été utilisé, le même jour, pour diagnostiquer une dépression majeure. Ce résultat a été utilisé pour évaluer les performances des deux tests de dépistage en calculant la sensibilité et la spécificité, notamment. Résultats Les données de 724 / 937 patients inclus ont pu être utilisées. Un diagnostic de dépression majeure a été posé chez 9.5% des patients (n = 69). La sensibilité et la spécificité des deux questions de dépistage étaient de 91.3% (IC95% : 81.4-96.4%) et 65.0% (IC95% : 61.2-68.6%), respectivement. En ajoutant la troisième question, la sensibilité des deux questions de dépistage a diminué à 59.4% (IC95% : 47.0-70.9%) et la spécificité a augmenté à 88.2% (IC95% : 85.4-90.5%). Conclusions L'utilisation des deux questions pour le dépistage de la dépression majeure est associée à une haute sensibilité et à une basse spécificité chez des patients se présentant en cabinet de médecine générale pour une plainte physique. En ajoutant la troisième question, la spécificité augmente, mais la sensibilité diminue. Ainsi, en ajoutant la troisième question, quatre patients dépressifs majeurs sur dix ne sont pas détectés, alors que seulement un patient sur dix n'est pas détecté avec les deux questions de dépistage. Notre étude montre que le test composé de deux questions reste une méthode de choix pour le dépistage de la dépression majeure et que l'ajout de la troisième question n'est pas recommandée. Celle-ci reste toutefois pertinente dans l'incitation au dialogue sur le sujet de la dépression entre le médecin et son patient.

Fast screening and confirmation of doping agents by UHPLC-QTOF-MS/MS

Introduction: The general strategy to perform anti-doping analysis starts with a screening followed by a confirmatory step when a sample is suspected to be positive. The screening step should be fast, generic and able to highlight any sample that may contain a prohibited substance by avoiding false negative and reducing false positive results. The confirmatory step is a dedicated procedure comprising a selective sample preparation and detection mode. Aim: The purpose of the study is to develop rapid screening and selective confirmatory strategies to detect and identify 103 doping agents in urine. Methods: For the screening, urine samples were simply diluted by a factor 2 with ultra-pure water and directly injected ("dilute and shoot") in the ultrahigh- pressure liquid chromatography (UHPLC). The UHPLC separation was performed in two gradients (ESI positive and negative) from 5/95 to 95/5% of MeCN/Water containing 0.1% formic acid. The gradient analysis time is 9 min including 3 min reequilibration. Analytes detection was performed in full scan mode on a quadrupole time-of-flight (QTOF) mass spectrometer by acquiring the exact mass of the protonated (ESI positive) or deprotonated (ESI negative) molecular ion. For the confirmatory analysis, urine samples were extracted on SPE 96-well plate with mixed-mode cation (MCX) for basic and neutral compounds or anion exchange (MAX) sorbents for acidic molecules. The analytes were eluted in 3 min (including 1.5 min reequilibration) with a S1-25 Ann Toxicol Anal. 2009; 21(S1) Abstracts gradient from 5/95 to 95/5% of MeCN/Water containing 0.1% formic acid. Analytes confirmation was performed in MS and MS/MS mode on a QTOF mass spectrometer. Results: In the screening and confirmatory analysis, basic and neutral analytes were analysed in the positive ESI mode, whereas acidic compounds were analysed in the negative mode. The analyte identification was based on retention time (tR) and exact mass measurement. "Dilute and shoot" was used as a generic sample treatment in the screening procedure, but matrix effect (e.g., ion suppression) cannot be avoided. However, the sensitivity was sufficient for all analytes to reach the minimal required performance limit (MRPL) required by the World Anti Doping Agency (WADA). To avoid time-consuming confirmatory analysis of false positive samples, a pre-confirmatory step was added. It consists of the sample re-injection, the acquisition of MS/MS spectra and the comparison to reference material. For the confirmatory analysis, urine samples were extracted by SPE allowing a pre-concentration of the analyte. A fast chromatographic separation was developed as a single analyte has to be confirmed. A dedicated QTOF-MS and MS/MS acquisition was performed to acquire within the same run a parallel scanning of two functions. Low collision energy was applied in the first channel to obtain the protonated molecular ion (QTOF-MS), while dedicated collision energy was set in the second channel to obtain fragmented ions (QTOF-MS/MS). Enough identification points were obtained to compare the spectra with reference material and negative urine sample. Finally, the entire process was validated and matrix effects quantified. Conclusion: Thanks to the coupling of UHPLC with the QTOF mass spectrometer, high tR repeatability, sensitivity, mass accuracy and mass resolution over a broad mass range were obtained. The method was sensitive, robust and reliable enough to detect and identify doping agents in urine. Keywords: screening, confirmatory analysis, UHPLC, QTOF, doping agents

Dépistage du cancer de la prostate: actualité. [Prostate cancer screening: an update]

Prostate cancer screening using PSA is controversial because of a low specificity and detection of non clinically relevant cancer. Two important studies have been published recently. One of two studies suggests a 20% lowering in specific prostate cancer mortality due to PSA screening. This benefit is relevant but implies at a high risk of overtreatment and treatment-related complications. Currently PSA screening is only proposed as an individual screening for informed patients.

Nouveautés en médecine ambutatoire: dépistage, traitement et iatrogénicité [Innovations in ambulatory care: screening, treatment and iatrogenicity]

Cette année, six études utiles pour la pratique ont été retenues. L'indication à la mammographie entre 40 et 49 ans devrait être évaluée individuellement et en tenant compte des risques/bénéfices de cet examen. Au-delà de 65 ans, un dépistage systématique de la fibrillation auriculaire avec prise de pouls puis ECG (si pouls irrégulier) pourrait être réalisé de manière systématique. Les risques de complications postcolonoscopie existent, particulièrement suite à des biopsies/polypectomies, et ce risque devrait être discuté. Les inhibiteurs de la pompe à protons au long court sont un facteur de risque de fracture de hanche. S'il est important de prendre en charge des pressions artérielles élevées au-delà de 80 ans, il faut être prudent (orthostatisme). Une corticothérapie précoce suite à une paralysie faciale périphérique est efficace. This year we have selected six studies useful for the day to day practice. A mammography in women 40 to 49 years of age should be evaluated taking into account the patient's profile and the possible risks and benefits of this exam. In patients over 65 years of age, a systematic atrial fibrillation screening, with pulse rate measuring then ECG (if irregular beat) should be realised on a regular basis. The risks for complications following colonoscopies do exist, especially after biopsies/polypectomies and this risk should be discussed. Long term proton pump inhibitor treatment is a risk factor for hip fracture. It is important to treat high blood pressure problems in the elderly, but the orthostatic risks should be adressed. A corticoid treatment started quickly for Bell's palsy is efficient

Prévention primaire et dépistage chez l'adulte: mise à jour 2010. [Prevention and screening in adults: trends in 2010].

This article proposes an update on the recommendations for the check-up and the primary and secondary prevention of cancers and cardio-vascular diseases. Indeed, new clinical data led the adaptation and clarification of some of them. The novelties for cancer screening concern mainly colorectal, breast and prostate cancers. Screening for low ankle brachial index is not recommended.

Docking, virtual high throughput screening and in silico fragment-based drug design.

ABSTRACT The drug discovery process has been profoundly changed recently by the adoption of computational methods helping the design of new drug candidates more rapidly and at lower costs. In silico drug design consists of a collection of tools helping to make rational decisions at the different steps of the drug discovery process, such as the identification of a biomolecular target of therapeutical interest, the selection or the design of new lead compounds and their modification to obtain better affinities, as well as pharmacokinetic and pharmacodynamic properties. Among the different tools available, a particular emphasis is placed in this review on molecular docking, virtual high throughput screening and fragment-based ligand design.

Serum-Mediane von Placentaprotein-Markern: Relevanz der Unterschiede zwischen spontanen und nach-in-vitro-Fertilisation eingetretenen Schwangerschaften für das fetale Trisomie-Screening.

Trisomy-21 (Down syndrome) is the most frequent chromosomal abnorm- ality but only one third of cases would be detected by amniocentesis based on maternal age alone. Serum screening tests in the early second trimester increase the detec- tion rate to 60-65%, and more recently it was found that such screening was also possible in the first trimester by quantifying a diffe- rent panel of markers. The concen- trations of these placental proteins are strongly dependent on gestatio- nal age; thus control medians must be established and precise dating is essential. Serum chorionic gonado- trophin (HCG) levels were recently found to be increased in IVF preg- nancies compared to spontaneous gestations, leading to a falsely ele- vated trisomy screening risk. The aim of this preliminary study was to find out whether, in the first-trime- ster screening, the markers similarly differed between IVF and spontane- ous pregnancies which would call for the establishment of separate normal medians for IVF patients. We compared 24 pregnancies ob- tained after ovarian stimulation and IVF with six women after thawed embryo transfer (unstimulated cycle) and 63 gestation- and maternal-age matched spontaneously pregnant controls. A single serum was ob- tained between 6 and 16 weeks of gestation and various placental protein levels determined by im- munometric assays. Serum levels of pregnancy-associated plasma protein A (PAPP-A), which is the major marker in the first-trimes- ter screening test, were reduced in IVF pregnancies: after 9 weeks of gestation, multiples of median (MoMs) ranged between 0.23 and 3.58 (logarithmic mean 0.743). For the frozen/thawed transfers, this value was 1.08. In the 9-12 week group containing 6 cases of IVF, three thawed transfers and 25 con- trols, PAPP-A was significantly redu- ced in the stimulated compared to the nonstimulated cycles. In the late first and early second trimester the difference was not significant in our small group but the trend persisted. Pregnancies after IVF will thus show an increased incidence of false positive results in fetal trisomy-21 screening, and special medians should be established for these pati- ents.

IRF6 Screening of Syndromic and a priori Non-Syndromic Cleft Lip and Palate Patients: Identification of a New Type of Minor VWS Sign.

Van der Woude syndrome (VWS), caused by dominant IRF6 mutation, is the most common cleft syndrome. In 15% of the patients, lip pits are absent and the phenotype mimics isolated clefts. Therefore, we hypothesized that some of the families classified as having non-syndromic inherited cleft lip and palate could have an IRF6 mutation. We screened in total 170 patients with cleft lip with or without cleft palate (CL/P): 75 were syndromic and 95 were a priori part of multiplex non-syndromic families. A mutation was identified in 62.7 and 3.3% of the patients, respectively. In one of the 95 a priori non-syndromic families with an autosomal dominant inheritance (family B), new insights into the family history revealed the presence, at birth, of lower lip pits in two members and the diagnosis was revised as VWS. A novel lower lip sign was observed in one individual in this family. Interestingly, a similar lower lip sign was also observed in one individual from a 2nd family (family A). This consists of 2 nodules below the lower lip on the external side. In a 3rd multiplex family (family C), a de novo mutation was identified in an a priori non-syndromic CL/P patient. Re-examination after mutation screening revealed the presence of a tiny pit-looking lesion on the inner side of the lower lip leading to a revised diagnosis of VWS. On the basis of this data, we conclude that IRF6 should be screened when any doubt rises about the normality of the lower lip and also if a non-syndromic cleft lip patient (with or without cleft palate) has a family history suggestive of autosomal dominant inheritance.

Screening for elevated blood pressure in children and adolescents: a critical appraisal.

Although screening for elevated blood pressure (BP) in adults is beneficial, evidence of its beneficial effects in children is not clear. Elevated BP in children is associated with atherosclerosis early in life and tracks across the life course. However, because of the high variability in BP, tracking is weak, and having an elevated BP in childhood has a low predictive value for having elevated BP later in life. The absolute risk of cardiovascular diseases associated with a given level of BP in childhood and the long-term effect of treatment beginning in childhood are not known. No study has experimentally evaluated the benefits and harm of BP screening in children. One modeling study indicates that BP screen-and-treat strategies in adolescents are moderately cost-effective but less cost-effective than population-wide interventions to decrease BP for the reduction of coronary heart diseases. The US National Heart, Lung, and Blood Institute and the European Society of Hypertension recommend that children 3 years of age and older have their BP measured during every health care visit. According to the US Preventive Services Task Force, there is no sufficient evidence to recommend for or against screening, but their recommendations have to be updated. Whether the benefits of universal BP screening in children outweigh the harm has to be determined. Studies are needed to assess the absolute risk of cardiovascular diseases associated with elevated BP in childhood, to evaluate how to simplify the identification of elevated BP, to evaluate the long-term benefits and harm of treatment beginning in childhood, and to compare universal and targeted screening strategies.

Screening of Asteraceae (Compositae) Plant Extracts for Larvicidal Activity against Aedes fluviatilis (Diptera: Culicidae)

Ethanol extracts of 83 plants species belonging to the Asteraceae (Compositae) family, collected in the State of Minas Gerais, Brazil, were tested for larvicidal activity against the mosquito Aedes fluviatilis - Diptera: Culicidae). The extract from Tagetes minuta was the most active with a LC90 of 1.5 mg/l and LC50 of 1.0 mg/l. This plant has been the object of several studies by other groups and its active components have already been identified as thiophene derivatives, a class of compounds present in many Asteraceae species. The extract of Eclipta paniculata was also significantly active, with a LC90 of 17.2 mg/l and LC50 of 3.3 mg/l and no previous studies on its larvicidal activity or chemical composition could be found in the literature. Extracts of Achryrocline satureoides, Gnaphalium spicatum, Senecio brasiliensis, Trixis vauthieri, Tagetes patula and Vernonia ammophila were less active, killing more than 50% of the larvae only at the higher dose tested (100 mg/l).

Abrupt decrease in serum testosterone levels after an oral glucose load in men: implications for screening for hypogonadism.

OBJECTIVE: This study examines the physiological impact of a glucose load on serum testosterone (T) levels in men with varying glucose tolerance (GT). DESIGN: Cross-sectional study. PATIENTS AND METHODS: 74 men (19-74 years, mean 51·4 ± 1·4 years) underwent a standard 75-g oral glucose tolerance test with blood sampling at 0, 30, 60, 90 and 120 min. Fasting serum glucose, insulin, total T (and calculated free T), LH, SHBG, leptin and cortisol were measured. RESULTS: 57% of the men had normal GT, 30% had impaired GT and 13% had newly diagnosed type 2 diabetes. Glucose ingestion was associated with a 25% decrease in mean T levels (delta = -4·2 ± 0·3 nm, P < 0·0001). T levels remained suppressed at 120 min compared with baseline (13·7 ± 0·6 vs 16·5 ± 0·7 nm, P < 0·0001) and did not differ across GT or BMI. Of the 66 men with normal T levels at baseline, 10 (15%) had levels that decreased to the hypogonadal range (<9·7 nm) at one or more time points. SHBG, LH and cortisol levels were unchanged. Leptin levels decreased from baseline at all time points (P < 0·0001). CONCLUSIONS: Glucose ingestion induces a significant reduction in total and free T levels in men, which is similar across the spectrum of glucose tolerance. This decrease in T appears to be because of a direct testicular defect, but the absence of compensatory changes in LH suggests an additional central component. Men found to have low nonfasting T levels should be re-evaluated in the fasting state.

Patent policy, patent pools, and the accumulation of claims in sequential innovation

We present a dynamic model where the accumulation of patents generates an increasing number of claims on sequential innovation. We compare innovation activity under three regimes -patents, no-patents, and patent pools- and find that none of them can reach the first best. We find that the first best can be reached through a decentralized tax-subsidy mechanism, by which innovators receive a subsidy when they innovate, and are taxed with subsequent innovations. This finding implies that optimal transfers work in the exact opposite way as traditional patents. Finally, we consider patents of finite duration and determine the optimal patent length.