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BackgroundThe effects of low-dose CT screening on disease stage shift, mortality and overdiagnosis are unclear. Lung cancer findings and mortality rates are reported at the end of screening in the Danish Lung Cancer Screening Trial.Methods4104 men and women, healthy heavy smokers/former smokers were randomised to five annual low-dose CT screenings or no screening. Two experienced chest radiologists read all CT scans and registered the location, size and morphology of nodules. Nodules between 5 and 15 mm without benign characteristics were rescanned after 3 months. Growing nodules (>25% volume increase and/or volume doubling time<400 days) and nodules >15 mm were referred for diagnostic workup. In the control group, lung cancers were diagnosed and treated outside the study by the usual clinical practice.ResultsParticipation rates were high in both groups (screening: 95.5%; control: 93.0%; p<0.001). Lung cancer detection rate was 0.83% at baseline and mean annual detection rate was 0.67% at incidence rounds (p=0.535). More lung cancers were diagnosed in the screening group (69 vs 24, p<0.001), and more were low stage (48 vs 21 stage I–IIB non-small cell lung cancer (NSCLC) and limited stage small cell lung cancer (SCLC), p=0.002), whereas frequencies of high-stage lung cancer were the same (21 vs 16 stage IIIA–IV NSCLC and extensive stage SCLC, p=0.509). At the end of screening, 61 patients died in the screening group and 42 in the control group (p=0.059). 15 and 11 died of lung cancer, respectively (p=0.428).ConclusionCT screening for lung cancer brings forward early disease, and at this point no stage shift or reduction in mortality was observed. More lung cancers were diagnosed in the screening group, indicating some degree of overdiagnosis and need for longer follow-up.

Background We present the final results of the effect of lung cancer screening with low-dose CT on the smoking habits of participants in a 5-year screening trial. Methods The Danish Lung Cancer Screening Trial (DLCST) was a 5-year screening trial that enrolled 4104 subjects; 2052 were randomised to annual low-dose CT (CT group) and 2052 received no intervention (control group). Participants were current and ex-smokers (≥4 weeks abstinence from smoking) with a tobacco consumption of ≥20 pack years. Smoking habits were determined annually. Missing values for smoking status at the final screening round were handled using two different models. Results There were no statistically significant differences in annual smoking status between the CT group and control group. Overall the ex-smoker rates (CT + control group) significantly increased from 24% (baseline) to 37% at year 5 of screening (p<0.001). The annual point prevalence quit rate increased from 11% to 24% during the five screening rounds; the ex-smokers’ relapse rate remained stable, around 11%, across the same period. Conclusions Screening with low-dose CT had no extra effect on smoking status compared with the control group, but overall the screening programme probably promoted smoking cessation. Clinical Trial Registration: The DLCST is registered in Clinical Trials.gov Protocol Registration System (identification no. NCT00496977).

Background Reviews state that there is a room for improvements of smoking cessation (SC) intervention in general practice. Methods In 2005, all 61 general practitioners (GPs) in four municipalities in Copenhagen, Denmark, were invited to participate. Twenty-four GPs accepted and were cluster randomized to one of three groups: Group A, referral to group-based SC counselling (national model), n = 10; Group B, referral to internet-based SC programme (newly developed), n = 8; or Group C, no referral (‘do as usual’), n = 6. A total of 1518/1914 smokers were included, and 760 returned a questionnaire at 1-year follow-up. Results The participating GPs reported significantly more SC counselling than GPs who refused participation (P = 0.04). Self-reported point abstinence was 6.7% (40/600), 5.9% (28/476) and 5.7% (25/442) in Groups A, B and C, respectively. Only 40 smokers attended group-based SC counselling, and 75 logged in at the internet-based SC programme. In cluster analyses, we found no significant additional effect of referral to group-based (OR: 1.05; 95% CI: 0.6–1.8) or internet-based SC programmes (OR: 0.91; 95% CI: 0.6–1.4). Conclusions We found no additional effect on cessation rates of GPs' referring to group-based SC counselling or internet-based SC programme. This finding might, to some degree, be explained by the short time used by the GPs on SC counselling and the selection of the participating doctors.

The metabolism of toluene and the influence of small doses of ethanol were measured in eight male volunteers after gastrointestinal uptake, the toluene concentration in alveolar air and the urinary excretion of hippuric acid and ortho-cresol being used as the measures of metabolism. During toluene exposure to 2 mg · min⁻¹ for 3 h the alveolar toluene concentration was 0.07 (range 0— 0.11) mg · m⁻¹; exposure to 6 mg-min⁻¹ for 30 min increased the alveolar concentration to 0.9 (range 0.03— 2.6) mg · m⁻³. Ingestion of 0.08, 0.16, and 0.32 g of ethanol per kilogram of body weight during toluene exposure of 2 mg · min⁻¹ increased the alveolar concentration within 10 min, and maximal alveolar concentrations of 5 (SD 3), 24 (SD 11), and 39 (SD 28) mg · m⁻³ were reached after 30, 60, and 90 min for the three doses, respectively. Hippuric acid excretion was only decreased by an ethanol dose of 0.32 g · kg⁻¹. Very low doses of ethanol inhibit toluene metabolism, and the procedure is sensitive enough to measure metabolic interactions between solvents and other xenobiotics in humans.

The impact of occupational exposure to jet fuel on antipyrine elimination was studied in 91 fuel-filling attendants. The mean antipyrine clearance was enhanced to 68.4 (SD 19.5) ml/min during exposure to jet fuel compared to 57.9 (SD 18.1) ml/min after an exposure-free period of two to four weeks. The corresponding values for 47 office workers (referents) were 62.7 (SD 22.2) ml/min and 56.4 (SD 22.3) ml/min. The median jet fuel concentration in the breathing zone of the fuel-filling attendants was 31 (range 1—1 020) mg/m³. No known inducing factor could be identified in the work environment of the office workers. No difference in the concentration of aspartate aminotransferase and alkaline phosphatase in serum was found either within or between the groups. Our study indicates that jet fuel, which is a mixture of aliphatic and aromatic organic solvents resembling gasoline and white spirit, is an inducer of hepatic drug metabolism in man.

Lipid pneumonia has been observed in infants exposed by inhalation of oil or butter applied into the nose or throat as part of an old custom. We performed a case-control study to test the hypothesis, that this ancient tradition may be a predisposing factor to bronchiectasis. A case group of 59 patients with bronchiectasis and three control groups - 46 patients with COPD, 32 asthmatics, and 71 healthy Saudis - were questioned about possible risk factors of bronchiectasis including nasal or oral application of oil/butter at infancy. The risk of witnessed exposure to this old folk remedy was significantly higher among the cases than the controls (OR = 3.9 (1.7-8.8), (95% confidence interval) p < 0.001). Application of oil or butter into the nasal or oral cavity of infants may be a risk factor for bronchiectasis.

A 42-year-old woman who experienced more than 50 attacks of left-sided facial palsies after exposure to chlorocresol was studied. Only muscles around the left side of the mouth were affected. On neurophysiological testing during chlorocresol provocation the only abnormality was a loss of motor units during maximal contraction of the left orbicularis oris muscle. This could be explained by a peripheral as well as a central effect. Extensive electrophysiological examination without chlorocresol provocation excluded a preexisting generalised nerve disorder and other diagnostic procedures did not give evidence of pathology involving the left facial nerve. A hyperreactive mechanism causing a transient block of the left facial nerve is proposed.

We present calculations on the formation of 258Rf in the reaction 50Ti+208Pb within the Langevin framework. The initital stage after contact of the colliding nuclei is dominated by a drift in the center-of-mass direction, while the subsequent process of forming a compound nucleus is diffusion dominated. The probability for the composite system to diffuse over the inner saddle is obtained by performing Metropolis random walks in a five-dimensional potential-energy landscape.

We present calculations on the formation of 258 Rf in the reaction 50 Ti+ 208 Pb within the Langevin framework. The initital stage after contact of the colliding nuclei is dominated by a drift in the center-of-mass direction, while the subsequent process of forming a compound nucleus is diffusion dominated. The probability for the composite system to diffuse over the inner saddle is obtained by performing Metropolis random walks in a five-dimensional potential-energy landscape.

The transformation of a moderately excited heavy nucleus into two excited fission fragments is modeled as a strongly damped evolution of the nuclear shape. The resulting Brownian motion in the multi-dimensional deformation space is guided by the shape-dependent level density which has been calculated microscopically for each of nearly ten million shapes (given in the three-quadratic-surfaces parametrization) by using a previously developed combinatorial method that employs the same single-particle levels as those used for the calculation of the pairing and shell contributions to the five-dimensional macroscopic-microscopic potential-energy surface. The stochastic shape evolution is followed until a small critical neck radius is reached, at which point the mass, charge, and shape of the two proto-fragments are extracted. The available excitation energy is divided statistically on the basis of the microscopic level densities associated with the two distorted fragments. Specific fragment structure features may cause the distribution of the energy disvision to deviate significantly from expectations based on a Fermi-gas level density. After their formation at scission, the initially distorted fragments are being accelerated by their mutual Coulomb repulsion as their shapes relax to their equilibrium forms. The associated distortion energy is converted to additional excitation energy in the fully accelerated fragments. These subsequently undergo sequential neutron evaporation which is calculated using again the appropriate microscopic level densities. The resulting dependence of the mean neutron multiplicity on the fragment mass, as well as the dependence of on the initial excitation energy of the fissioning compound nucleus, exhibit features that are similar to the experimentally observed behavior, suggesting that the microscopic energy sharing mechanism plays an important role in low-energy fission.