Assessment of learning curves in complex surgical interventions: a consecutive case-series study

Background: Surgical interventions are complex, which complicates their rigorous assessment through randomised clinical trials. An important component of complexity relates to surgeon experience and the rate at which the required level of skill is achieved, known as the learning curve. There is considerable evidence that operator performance for surgical innovations will change with increasing experience. Such learning effects complicate evaluations; the start of the trial might be delayed, resulting in loss of surgeon equipoise or, if an assessment is undertaken before performance has stabilised, the true impact of the intervention may be distorted. Methods: Formal estimation of learning parameters is necessary to characterise the learning curve, model its evolution and adjust for its presence during assessment. Current methods are either descriptive or model the learning curve through three main features: the initial skill level, the learning rate and the final skill level achieved. We introduce a fourth characterising feature, the duration of the learning period, which provides an estimate of the point at which learning has stabilised. We propose a two-phase model to estimate formally all four learning curve features. Results: We demonstrate that the two-phase model can be used to estimate the end of the learning period by incorporating a parameter for estimating the duration of learning. This is achieved by breaking down the model into a phase describing the learning period and one describing cases after the final skill level is reached, with the break point representing the length of learning. We illustrate the method using cardiac surgery data. Conclusions: This modelling extension is useful as it provides a measure of the potential cost of learning an intervention and enables statisticians to accommodate cases undertaken during the learning phase and assess the intervention after the optimal skill level is reached. The limitations of the method and implications for the optimal timing of a definitive randomised controlled trial are also discussed

Effects of butter from mountain-pasture grazing cows on risk markers of the metabolic syndrome compared with conventional Danish butter: a randomized controlled study.

BACKGROUND: There is considerable interest in dairy products from low-input systems, such as mountain-pasture grazing cows, because these products are believed to be healthier than products from high-input conventional systems. This may be due to a higher content of bioactive components, such as phytanic acid, a PPAR-agonist derived from chlorophyll. However, the effects of such products on human health have been poorly investigated. OBJECTIVE: To compare the effect of milk-fat from mountain-pasture grazing cows (G) and conventionally fed cows (C) on risk markers of the metabolic syndrome. DESIGN: In a double-blind, randomized, 12-week, parallel intervention study, 38 healthy subjects replaced part of their habitual dietary fat intake with 39 g fat from test butter made from milk from mountain-pasture grazing cows or from cows fed conventional winter fodder. Glucose-tolerance and circulating risk markers were analysed before and after the intervention. RESULTS: No differences in blood lipids, lipoproteins, hsCRP, insulin, glucose or glucose-tolerance were observed. Interestingly, strong correlations between phytanic acid at baseline and total (P<0.0001) and LDL cholesterol (P=0.0001) were observed. CONCLUSIONS: Lack of effects on blood lipids and inflammation indicates that dairy products from mountain-pasture grazing cows are not healthier than products from high-input conventional systems. Considering the strong correlation between LDL cholesterol and phytanic acid at baseline, it may be suggested that phytanic acid increases total and LDL cholesterol. TRIAL REGISTRATION: ClinicalTrials.gov, NCT0134358

Developing a placebo-controlled trial in surgery:issues of design, acceptability and feasibility

BACKGROUND: Surgical placebos are controversial. This in-depth study explored the design, acceptability, and feasibility issues relevant to designing a surgical placebo-controlled trial for the evaluation of the clinical and cost effectiveness of arthroscopic lavage for the management of people with osteoarthritis of the knee in the UK. METHODS: Two surgeon focus groups at a UK national meeting for orthopaedic surgeons and one regional surgeon focus group (41 surgeons); plenary discussion at a UK national meeting for orthopaedic anaesthetists (130 anaesthetists); three focus groups with anaesthetists (one national, two regional; 58 anaesthetists); two focus groups with members of the patient organisation Arthritis Care (7 participants); telephone interviews with people on consultant waiting lists from two UK regional centres (15 participants); interviews with Chairs of UK ethics committees (6 individuals); postal surveys of members of the British Association of Surgeons of the Knee (382 surgeons) and members of the British Society of Orthopaedic Anaesthetists (398 anaesthetists); two centre pilot (49 patients assessed). RESULTS: There was widespread acceptance that evaluation of arthroscopic lavage had to be conducted with a placebo control if scientific rigour was not to be compromised. The choice of placebo surgical procedure (three small incisions) proved easier than the method of anaesthesia (general anaesthesia). General anaesthesia, while an excellent mimic, was more intrusive and raised concerns among some stakeholders and caused extensive discussion with local decision-makers when seeking formal approval for the pilot.Patients were willing to participate in a pilot with a placebo arm; although some patients when allocated to surgery became apprehensive about the possibility of receiving placebo, and withdrew. Placebo surgery was undertaken successfully. CONCLUSIONS: Our study illustrated the opposing and often strongly held opinions about surgical placebos, the ethical issues underpinning this controversy, and the challenges that exist even when ethics committee approval has been granted. It showed that a placebo-controlled trial could be conducted in principle, albeit with difficulty. It also highlighted that not only does a placebo-controlled trial in surgery have to be ethically and scientifically acceptable but that it also must be a feasible course of action. The place of placebo-controlled surgical trials more generally is likely to be limited and require specific circumstances to be met. Suggested criteria are presented. TRIAL REGISTRATION NUMBER: The trial was assigned ISRCTN02328576 through http://controlled-trials.com/ in June 2006. The first patient was randomised to the pilot in July 2007

Congenital and childhood atrioventricular blocks: pathophysiology and contemporary management

Atrioventricular block is classified as congeni- tal if diagnosed in utero, at birth, or within the first month of life. The pathophysiological process is believed to be due to immune-mediated injury of the conduction system, which occurs as a result of transplacental pas- sage of maternal anti-SSA/Ro-SSB/La antibodies. Childhood atrioventricular block is therefore diagnosed between the first month and the 18th year of life. Genetic variants in multiple genes have been described to date in the pathogenesis of inherited progressive car- diac conduction disorders. Indications and techniques of cardiac pacing have also evolved to allow safe perma- nent cardiac pacing in almost all patients, including those with structural heart abnormalities

CYP3A4 and CYP3A5 genotyping by Pyrosequencing

BACKGROUND: Human cytochrome P450 3A enzymes, particularly CYP3A4 and CYP3A5, play an important role in drug metabolism. CYP3A expression exhibits substantial interindividual variation, much of which may result from genetic variation. This study describes Pyrosequencing assays for key SNPs in CYP3A4 (CYP3A4*1B, CYP3A4*2, and CYP3A4*3) and CYP3A5 (CYP3A5*3C and CYP3A5*6). METHODS: Genotyping of 95 healthy European and 95 healthy African volunteers was performed using Pyrosequencing. Linkage disequilibrium, haplotype inference, Hardy-Weinberg equilibrium, and tag SNPs were also determined for these samples. RESULTS: CYP3A4*1B allele frequencies were 4% in Europeans and 82% in Africans. The CYP3A4*2 allele was found in neither population sample. CYP3A4*3 had an allele frequency of 2% in Europeans and 0% in Africans. The frequency of CYP3A5*3C was 94% in Europeans and 12% in Africans. No CYP3A5*6 variants were found in the European samples, but this allele had a frequency of 16% in the African samples. Allele frequencies and haplotypes show interethnic variation, highlighting the need to analyze clinically relevant SNPs and haplotypes in a variety of ethnic groups. CONCLUSION: Pyrosequencing is a versatile technique that could improve the efficiency of SNP analysis for pharmacogenomic research with the ultimate goal of pre-screening patients for individual therapy selection

Generating Bessel beams with broad depth-of-field by using phase-only acoustic holograms

[EN] We report zero-th and high-order acoustic Bessel beams with broad depth-of-field generated using acoustic holograms. While the transverse field distribution of Bessel beams generated using traditional passive methods is correctly described by a Bessel function, these methods present a common drawback: the axial distribution of the field is not constant, as required for ideal Bessel beams. In this work, we experimentally, numerically and theoretically report acoustic truncated Bessel beams of flat-intensity along their axis in the ultrasound regime using phase-only holograms. In particular, the beams present a uniform field distribution showing an elongated focal length of about 40 wavelengths, while the transverse width of the beam remains smaller than 0.7 wavelengths. The proposed acoustic holograms were compared with 3D-printed fraxicons, a blazed version of axicons. The performance of both phase-only holograms and fraxicons is studied and we found that both lenses produce Bessel beams in a wide range of frequencies. In addition, high-order Bessel beam were generated. We report first order Bessel beams that show a clear phase dislocation along their axis and a vortex with single topological charge. The proposed method may have potential applications in ultrasonic imaging, biomedical ultrasound and particle manipulation applications using passive lenses.This work was supported by the Spanish Ministry of Economy and Innovation (MINECO) through Project TEC2016-80976-R. NJ and SJ acknowledge financial support from Generalitat Valenciana through grants APOSTD/2017/042, ACIF/2017/045 and GV/2018/11. FC acknowledges financial support from Agencia Valenciana de la Innovacio through grant INNCON00/18/9 and European Regional Development Fund (IDIFEDER/2018/022).Jiménez-Gambín, S.; Jimenez, N.; Benlloch Baviera, JM.; Camarena Femenia, F. (2019). Generating Bessel beams with broad depth-of-field by using phase-only acoustic holograms. Scientific Reports. 9:1-13. https://doi.org/10.1038/s41598-019-56369-zS1139Durnin, J. Exact solutions for nondiffracting beams. i. the scalar theory. J. Opt. Soc. Am. A 4, 651 (1987).Durnin, J., Miceli, J. Jr & Eberly, J. Diffraction-free beams. Physical review letters 58, 1499 (1987).Chu, X. Analytical study on the self-healing property of Bessel beam. Eur. Phys. J. D 66, 259 (2012).McLeod, E., Hopkins, A. B. & Arnold, C. B. Multiscale Bessel beams generated by a tunable acoustic gradient index of refraction lens. Opt. Lett. 31, 3155 (2006).Li, Z., Alici, K. B., Caglayan, H. & Ozbay, E. Generation of an axially asymmetric Bessel-like beam from a metallic subwavelength aperture. Phys. Rev. Lett. 102, 143901 (2009).Fahrbach, F. & Rohrbach, A. Propagation stability of self-reconstructing Bessel beams enables contrast-enhanced imaging in thick media. Nat. Commun. 3, 632 (2011).Lu, J.-y, Zou, H. & Greenleaf, J. F. Biomedical ultrasound beam forming. Ultrasound in medicine & biology 20, 403–428 (1994).Marston, P. L. Scattering of a Bessel beam by a sphere. J. Acous. Soc. Am. 121, 753 (2007).Marston, P. L. Scattering of a Bessel beam by a sphere: Ii. helicoidal case and spherical shell example. The Journal of the Acoustical Society of America 124, 2905–2910 (2008).Lu, J. & Greenleaf, F. Ultrasonic nondiffracting transducer for medical imaging. IEEE Trans. Ultrason. Ferroelec. Freq. Contr. 37, 438 (1990).Lu, J.-Y. & Greenleaf, J. F. Pulse-echo imaging using a nondiffracting beam transducer. Ultrasound in medicine & biology 17, 265–281 (1991).Lu, J.-y, Song, T.-K., Kinnick, R. R. & Greenleaf, J. F. In vitro and in vivo real-time imaging with ultrasonic limited diffraction beams. IEEE transactions on medical imaging 12, 819–829 (1993).Lu, J.-y, Xu, X.-L., Zou, H. & Greenleaf, J. F. Application of Bessel beam for doppler velocity estimation. IEEE transactions on ultrasonics, ferroelectrics, and frequency control 42, 649–662 (1995).Nabavizadeh, A., Greenleaf, J. F., Fatemi, M. & Urban, M. W. Optimized shear wave generation using hybrid beamforming methods. Ultrasound in medicine & biology 40, 188–199 (2014).Marston, P. L. Axial radiation force of a Bessel beam on a sphere and direction reversal of the force. The Journal of the Acoustical Society of America 120, 3518–3524 (2006).Marston, P. L. Negative axial radiation forces on solid spheres and shells in a Bessel beam. The Journal of the Acoustical Society of America 122, 3162–3165 (2007).Marston, P. L. Radiation force of a helicoidal Bessel beam on a sphere. The Journal of the Acoustical Society of America 125, 3539–3547 (2009).Thomas, J.-L. & Marchiano, R. Pseudo angular momentum and topological charge conservation for nonlinear acoustical vortices. Physical review letters 91, 244302 (2003).Volke-Sepúlveda, K., Santillán, A. O. & Boullosa, R. R. Transfer of angular momentum to matter from acoustical vortices in free space. Phys. Rev. Lett. 100, 024302 (2008).Zhang, L. & Marston, P. L. Geometrical interpretation of negative radiation forces of acoustical Bessel beams on spheres. Physical Review E 84, 035601 (2011).Courtney, C. R. et al. Dexterous manipulation of microparticles using Bessel-function acoustic pressure fields. Applied Physics Letters 102, 123508 (2013).Hong, Z., Zhang, J. & Drinkwater, B. W. Observation of orbital angular momentum transfer from Bessel-shaped acoustic vortices to diphasic liquid-microparticle mixtures. Phys. Rev. Lett. 114, 214301 (2015).Baresch, D., Thomas, J.-L. &Marchiano, R. Observation of a single-beam gradient force acoustical trap for elastic particles: Acoustical tweezers. Phys. Rev. Lett. 116 (2016).Marzo, A., Caleap, M. & Drinkwater, B. W. Acoustic virtual vortices with tunable orbital angular momentum for trapping of mie particles. Phys. Rev. Lett. 120, 044301 (2018).Li, Y. et al. Acoustic radiation torque of an acoustic-vortex spanner exerted on axisymmetric objects. Applied Physics Letters 112, 254101 (2018).Riaud, A., Baudoin, M., Thomas, J.-L. & Matar, O. B. Cyclones and attractive streaming generated by acoustical vortices. Physical Review E 90, 013008 (2014).Shi, C., Dubois, M., Wang, Y. & Zhang, X. High-speed acoustic communication by multiplexing orbital angular momentum. Proceedings of the National Academy of Sciences 114, 7250–7253 (2017).Jiang, X., Liang, B., Cheng, J.-C. & Qiu, C.-W. Twisted acoustics: metasurface-enabled multiplexing and demultiplexing. Advanced Materials 30, 1800257 (2018).Hsu, D., Margetan, F. & Thompson, D. O. Bessel beam ultrasonic transducer: fabrication method and experimental results. Appl. Phys. Lett. 55, 2066 (1989).Campbell, J. A. & Soloway, S. Generation of a nondiffracting beam with frequency-independent beamwidth. The Journal of the Acoustical Society of America 88, 2467–2477 (1990).Masuyama, H., Yokoyama, T., Nagai, K. & Mizutani, K. Generation of Bessel beam from equiamplitude-driven annular transducer array consisting of a few elements. Jpn. J. Appl. Phys. 38, 3080 (1999).Fjield, T., Fan, X. & Hynynen, K. A parametric study of the concentric-ring transducer design for mri guided ultrasound surgery. J. Acoust. Soc. Am. 100, 1220 (1996).Chillara, V. K., Pantea, C. & Sinha, D. N. Low-frequency ultrasonic Bessel-like collimated beam generation from radial modes of piezoelectric transducers. Applied Physics Letters 110, 064101 (2017).Burckhardt, C., Hoffmann, H. & Grandchamp, P.-A. Ultrasound axicon: A device for focusing over a large depth. The Journal of the Acoustical Society of America 54, 1628–1630 (1973).Foster, F., Patterson, M., Arditi, M. & Hunt, J. The conical scanner: a two transducer ultrasound scatter imaging technique. Ultrasonic imaging 3, 62–82 (1981).McLeod, J. H. The axicon: A new type of optical element. J. Opt. Soc. Am. 44, 592 (1954).Arlt, J. & Dholakia, K. Generation of high-order Bessel beams by use of an axicon. Optics Communications 177, 297–301 (2000).Golub, I. Fresnel axicon. Optics letters 31, 1890–1892 (2006).Lirette, R. & Mobley, J. Broadband wave packet dynamics of minimally diffractive ultrasonic fields from axicon and stepped fraxicon lenses. The Journal of the Acoustical Society of America 146, 103–108 (2019).Jiménez, N. et al. Acoustic Bessel-like beam formation by an axisymmetric grating. Europhys. Lett. 106, 24005 (2014).Xu, Z., Xu, W., Qian, M., Cheng, Q. & Liu, X. A flat acoustic lens to generate a Bessel-like beam. Ultrasonics 80, 66–71 (2017).Li, Y., Liang, B., Gu, Z.-M., Zou, X.-Y. & Cheng, J.-C. Reflected wavefront manipulation based on ultrathin planar acoustic metasurfaces. Scientific Reports 3, 2546 (2013).Nye, J. & Berry, M. Dislocations in wave trains. Proc. R. Soc. London, Ser. A 336, 165–190 (1974).Jiménez, N. et al. Formation of high-order acoustic Bessel beams by spiral diffraction gratings. Physical Review E 94, 053004 (2016).Wang, T. et al. Particle manipulation with acoustic vortex beam induced by a brass plate with spiral shape structure. Applied Physics Letters 109, 123506 (2016).Jia, Y.-R., Wei, Q., Wu, D.-J., Xu, Z. & Liu, X.-J. Generation of fractional acoustic vortex with a discrete archimedean spiral structure plate. Applied Physics Letters 112, 173501 (2018).Jiménez, N., Romero-Garca, V., Garca-Raffi, L. M., Camarena, F. & Staliunas, K. Sharp acoustic vortex focusing by fresnel-spiral zone plates. Applied Physics Letters 112, 204101 (2018).Baudoin, M. et al. Folding a focalized acoustical vortex on a flat holographic transducer: miniaturized selective acoustical tweezers. Science advances 5, eaav1967 (2019).Muelas-Hurtado, R. D., Ealo, J. L., Pazos-Ospina, J. F. & Volke-Sepúlveda, K. Acoustic analysis of a broadband spiral source for the simultaneous generation of multiple Bessel vortices in air. The Journal of the Acoustical Society of America 144, 3252–3261 (2018).Muelas-Hurtado, R. D., Ealo, J. L., Pazos-Ospina, J. F. & Volke-Sepúlveda, K. Generation of multiple vortex beam by means of active diffraction gratings. Applied Physics Letters 112, 084101 (2018).Wunenburger, R., Lozano, J. I. V. & Brasselet, E. Acoustic orbital angular momentum transfer to matter by chiral scattering. New Journal of Physics 17, 103022 (2015).Terzi, M., Tsysar, S., Yuldashev, P., Karzova, M. & Sapozhnikov, O. Generation of a vortex ultrasonic beam with a phase plate with an angular dependence of the thickness. Moscow University Physics Bulletin 72, 61–67 (2017).Hefner, B. T. & Marston, P. L. An acoustical helicoidal wave transducer with applications for the alignment of ultrasonic and underwater systems. Jour. Acous. Soc. Am. 106, 3313–3316 (1999).Ealo, J. L., Prieto, J. C. & Seco, F. Airborne ultrasonic vortex generation using flexible ferroelectrets. IEEE transactions on ultrasonics, ferroelectrics, and frequency control 58, 1651–1657 (2011).Naify, C. J. et al. Generation of topologically diverse acoustic vortex beams using a compact metamaterial aperture. Applied Physics Letters 108, 223503 (2016).Ye, L. et al. Making sound vortices by metasurfaces. AIP Advances 6, 085007 (2016).Jiang, X., Li, Y., Liang, B., Cheng, J.-C. & Zhang, L. Convert acoustic resonances to orbital angular momentum. Physical review letters 117, 034301 (2016).Esfahlani, H., Lissek, H. & Mosig, J. R. Generation of acoustic helical wavefronts using metasurfaces. Physical Review B 95, 024312 (2017).Jiménez-Gambn, S., Jiménez, N., Benlloch, J. M. & Camarena, F. Holograms to focus arbitrary ultrasonic fields through the skull. Physical Review Applied 12, 014016 (2019).Maimbourg, G., Houdouin, A., Deffieux, T., Tanter, M. & Aubry, J.-F. 3d-printed adaptive acoustic lens as a disruptive technology for transcranial ultrasound therapy using single-element transducers. Physics in Medicine & Biology 63, 025026 (2018).Ferri, M. et al. On the evaluation of the suitability of the materials used to 3d print holographic acoustic lenses to correct transcranial focused ultrasound aberrations. Polymers 11, 1521 (2019).Melde, K., Mark, A. G., Qiu, T. & Fischer, P. Holograms for acoustics. Nature 537, 518 (2016).Brown, M. D., Cox, B. T. & Treeby, B. E. Design of multi-frequency acoustic kinoforms. Applied Physics Letters 111, 244101 (2017).Brown, M., Nikitichev, D., Treeby, B. & Cox, B. Generating arbitrary ultrasound fields with tailored optoacoustic surface profiles. Applied Physics Letters 110, 094102 (2017).Zhu, Y. et al. Fine manipulation of sound via lossy metamaterials with independent and arbitrary reflection amplitude and phase. Nature communications 9, 1632 (2018).Brown, M. D. Phase and amplitude modulation with acoustic holograms. Applied Physics Letters 115, 053701 (2019).Jiménez, N., Romero-Garca, V., Pagneux, V. & Groby, J.-P. Quasiperfect absorption by subwavelength acoustic panels in transmission using accumulation of resonances due to slow sound. Physical Review B 95, 014205 (2017).Tsang, P. W. M. & Poon, T.-C. Novel method for converting digital fresnel hologram to phase-only hologram based on bidirectional error diffusion. Optics Express 21, 23680–23686 (2013).Soret, J. Ueber die durch kreisgitter erzeugten diffractionsphänomene. Annalen der Physik 232, 99–113 (1875).Turunen, J., Vasara, A. & Friberg, A. T. Holographic generation of diffraction-free beams. Applied Optics 27, 3959–3962 (1988).Vasara, A., Turunen, J. & Friberg, A. T. Realization of general nondiffracting beams with computer-generated holograms. JOSA A 6, 1748–1754 (1989).Cunningham, K. B. & Hamilton, M. F. Bessel beams of finite amplitude in absorbing fluids. J. Acous. Soc. Am. 108, 519 (2000).Ding, D. & Y. Lu, J. Higher-order harmonics of limited diffraction Bessel beams. J. Acous. Soc. Am. 107, 1212 (2000).Skeldon, K., Wilson, C., Edgar, M. & Padgett, M. An acoustic spanner and its associated rotational Doppler shift. New J. Phys. 10, 013018 (2008).Wu, J. Acoustical tweezers. J. Acoust. Soc. Am. 89, 2140–2143 (1991).Zhang, L. & Marston, P. L. Angular momentum flux of nonparaxial acoustic vortex beams and torques on axisymmetric objects. Physical Review E 84, 065601 (2011).Yoon, C., Kang, B. J., Lee, C., Kim, H. H. & Shung, K. K. Multi-particle trapping and manipulation by a high-frequency array transducer. Appl. Phys. Lett. 105, 214103 (2014).Marzo, A. et al. Holographic acoustic elements for manipulation of levitated objects. Nat. Commun. 6 (2015).Blackstock, D. T. Fundamentals of physical acoustics (John Wiley & Sons, 2000).Treeby, B. E. & Cox, B. Modeling power law absorption and dispersion for acoustic propagation using the fractional laplacian. The Journal of the Acoustical Society of America 127, 2741–2748 (2010).Treeby, B. E., Jaros, J., Rendell, A. P. & Cox, B. Modeling nonlinear ultrasound propagation in heterogeneous media with power law absorption using a k-space pseudospectral method. The Journal of the Acoustical Society of America 131, 4324–4336 (2012).Jiménez, N. et al. Time-domain simulation of ultrasound propagation in a tissue-like medium based on the resolution of the nonlinear acoustic constitutive relations. Acta Acustica united with Acustica 102, 876–892 (2016)

Does self-management for return to work increase the effectiveness of vocational rehabilitation for chronic compensated musculoskeletal disorders? - Protocol for a randomised controlled trial

Musculoskeletal disorders are common and costly disorders to workers compensation and motor accident insurance systems and are a leading contributor to the burden of ill-health. In Australia, vocational rehabilitation is provided to workers to assist them to stay in or return to work. Self-management training may be an innovative addition to improve health and employment outcomes from vocational rehabilitation

Smoking among pregnant women in Cantabria (Spain): trend and determinants of smoking cessation

Background Cantabria (Spain) has one of the highest prevalence of smoking among women of the European Union. The objectives are to assess the trend of smoking during pregnancy in a five-year period and the determinants of smoking cessation during pregnancy in Cantabria. Methods A 1/6 random sample of all women delivering at the reference hospital of the region for the period 1998–2002 was drawn, 1559 women. Information was obtained from personal interview, clinical chart, and prenatal care records. In the analysis relative risks and 95% confidence intervals were estimated. Multivariable analysis was carried out using stepwise logistic regression. Results Smoking prior to pregnancy decreased from 53.6% in 1998 to 39.4% in 2002. A decrease in smoking cessation among women smoking at the beginning of pregnancy was observed, from 37.3% in 1998 to 20.6% in 2002. The mean number of cigarettes/day (cig/d) before pregnancy remained constant, around 16 cig/d, whereas a slight trend to increase over time was seen, from 7.7 to 8.9 cig/d. In univariate analysis two variables favoured significantly smoking cessation, although they were not included in the stepwise logistic regression analysis, a higher education level and to be married. The logistic regression model included five significant predictors (also significant in univariate analysis): intensity of smoking, number of previous pregnancies, partner's smoking status, calendar year of study period (these four variables favoured smoking continuation), and adequate prenatal care (which increased smoking cessation). Conclusion The frequency of smoking among pregnant women is very high in Cantabria. As smoking cessation rate has decreased over time, a change in prenatal care programme on smoking counseling is needed. Several determinants of smoking cessation, such as smoking before pregnancy and partner's smoking, should be also addressed by community programmes

Evaluation of variants in the selectin genes in age-related macular degeneration

<p>Abstract</p> <p>Background</p> <p>Age-related macular degeneration (AMD) is a common disease of the elderly that leads to loss of the central visual field due to atrophic or neovascular events. Evidence from human eyes and animal models suggests an important role for macrophages and endothelial cell activation in the pathogenesis of AMD. We sought to determine whether common ancestral variants in genes encoding the selectin family of proteins are associated with AMD.</p> <p>Methods</p> <p>Expression of E-selectin, L-selectin and P-selectin was examined in choroid and retina by quantitative PCR and immunofluorescence. Samples from patients with AMD (n = 341) and controls (n = 400) were genotyped at a total of 34 SNPs in the <it>SELE</it>, <it>SELL </it>and <it>SELP </it>genes. Allele and genotype frequencies at these SNPs were compared between AMD patients and controls as well as between subtypes of AMD (dry, geographic atrophy, and wet) and controls.</p> <p>Results</p> <p>High expression of all three selectin genes was observed in the choroid as compared to the retina. Some selectin labeling of retinal microglia, drusen cores and the choroidal vasculature was observed. In the genetic screen of AMD versus controls, no positive associations were observed for <it>SELE </it>or <it>SELL</it>. One SNP in <it>SELP </it>(rs3917751) produced p-values < 0.05 (uncorrected for multiple measures). In the subtype analyses, 6 SNPs (one in <it>SELE</it>, two in <it>SELL</it>, and three in <it>SELP</it>) produced p-values < 0.05. However, when adjusted for multiple measures with a Bonferroni correction, only one SNP in <it>SELP </it>(rs3917751) produced a statistically significant p-value (p = 0.0029).</p> <p>Conclusions</p> <p>This genetic screen did not detect any SNPs that were highly associated with AMD affection status overall. However, subtype analysis showed that a single SNP located within an intron of <it>SELP </it>(rs3917751) is statistically associated with dry AMD in our cohort. Future studies with additional cohorts and functional assays will clarify the biological significance of this discovery. Based on our findings, it is unlikely that common ancestral variants in the other selectin genes (<it>SELE </it>and <it>SELL</it>) are risk factors for AMD. Finally, it remains possible that sporadic or rare mutations in <it>SELE</it>, <it>SELL</it>, or <it>SELP </it>have a role in the pathogenesis of AMD.</p

Evaluation of a 'virtual' approach to commissioning health research

BACKGROUND: The objective of this study was to evaluate the implementation of a 'virtual' (computer-mediated) approach to health research commissioning. This had been introduced experimentally in a DOH programme – the 'Health of Londoners Programme' – in order to assess whether is could enhance the accessibility, transparency and effectiveness of commissioning health research. The study described here was commissioned to evaluate this novel approach, addressing these key questions. METHODS: A naturalistic-experimental approach was combined with principles of action research. The different commissioning groups within the programme were randomly allocated to either the traditional face-to-face mode or the novel 'virtual' mode. Mainly qualitative data were gathered including observation of all (virtual and face-to-face) commissioning meetings; semi-structured interviews with a purposive sample of participants (n = 32/66); structured questionnaires and interviews with lead researchers of early commissioned projects. All members of the commissioning groups were invited to participate in collaborative enquiry groups which participated actively in the analysis process. RESULTS: The virtual process functioned as intended, reaching timely and relatively transparent decisions that participants had confidence in. Despite the potential for greater access using a virtual approach, few differences were found in practice. Key advantages included physical access, a more flexible and extended time period for discussion, reflection and information gathering and a more transparent decision-making process. Key challenges were the reduction of social cues available in a computer-mediated medium that require novel ways of ensuring appropriate dialogue, feedback and interaction. However, in both modes, the process was influenced by a range of factors and was not technology driven. CONCLUSION: There is potential for using computer-mediated communication within the research commissioning process. This may enhance access, effectiveness and transparency of decision-making but further development is needed for this to be fully realised, including attention to process as well as the computer-mediated medium