Five-year results of the complete versus culprit vessel percutaneous coronary intervention in multivessel disease using drug-eluting stents II (CORRECT II) study: a prospective, randomised controlled trial.

OBJECTIVES/BACKGROUND: In patients with multivessel coronary artery disease (MVD) the decision whether to treat a single culprit vessel or to perform multivessel revascularisation may be challenging. The purpose of this study was to evaluate the long-term outcome of multivessel percutaneous coronary intervention (MV-PCI) versus culprit vessel only (CV-PCI) in patients with stable coronary artery disease or non-ST elevation acute coronary syndrome. METHODS: In this dual-centre, prospective, randomised study a total 215 patients with MVD were randomly assigned to MV-PCI or CV-PCI. The primary endpoint was the occurrence of major adverse cardiac events (MACE) including death, myocardial infarction (MI), and repeat revascularisation. Secondary endpoints were the combined endpoint of death or MI, the individual components of the primary endpoint, and the occurrence of stent thrombosis. Patients were followed up to 5 years after enrolment. RESULTS: The occurrence of the primary endpoint was similar at 28% versus 31% in the MV-PCI and CV-PCI group, respectively (hazard ratio [HR] 0.87, 95% confidence interval [CI]: 0.53-1.44, p = 0.59). The rate of repeat revascularisation was 15% versus 24% (HR 0.59, 95% CI 0.32 to 1.11, p = 0.11), whereas definite or probable stent thrombosis occurred in 2% versus 0% (p = 0.44). CONCLUSIONS: In this randomised study comparing the strategies for MV-PCI and CV-PCI in patients with MVD, no difference was found in the occurrence of MACE after 5 years. We observed a numerically higher rate of death or MI and a lower rate of repeat revascularisation after MV-PCI, although these findings were not statistically significant.

Impact of percutaneous coronary intervention timing on 5-year outcome in patients with non-ST-segment elevation acute coronary syndromes. The 'wait a day' approach might be safer.

BACKGROUND: The OPTIMA trial was a randomised multicentre trial exploring the influence of the timing of percutaneous coronary intervention (PCI) on patient outcomes in an intermediate to high risk non-ST-elevation acute coronary syndrome (NSTE-ACS) population. In order to decide the best treatment strategy for patients presenting with NSTE-ACS, long-term outcomes are essential. METHODS: Five-year follow-up data from 133 of the 142 patients could be retrieved (94 %). The primary endpoint was a composite of death and spontaneous myocardial infarction (MI). Spontaneous MI was defined as MI occurring more than 30 days after randomisation. Secondary endpoints were the individual outcomes of death, spontaneous MI or re-PCI. RESULTS: No significant difference with respect to the primary endpoint was observed (17.8 vs. 10.1 %; HR 1.55, 95 % CI: 0.73-4.22, p = 0.21). There was no significant difference in mortality rate. However, spontaneous MI was significantly more common in the group receiving immediate PCI (11.0 vs. 1.4 %; HR 4.46, 95 % CI: 1.21-16.50, p = 0.02). We did not find a significant difference between the groups with respect to re-PCI rate. CONCLUSION: There was no difference in the composite of death and spontaneous MI. The trial suggests an increased long-term risk of spontaneous MI for patients treated with immediate PCI.

I'll be there for you: The effects of exercise engagement on social support provision within undergraduate students' personal networks.

Objective: To use social network analysis to examine exercise participation relative to health and wellness support provision within students' networks. Participants: 513 undergraduates from a large private university completed online surveys. Methods: Multilevel modeling assessed exercise engagement at the individual and dyadic level and support provision from network members. Results: More support was perceived by first and second-year students and individuals who reported more exercise engagement. Significant others, roommates, siblings, female network members, and those who exercised often provided greater support. Greater support was reported when both the participant and their social tie were involved in the campus group-exercise program. Conclusion: This study suggests individual and dyadic-level exercise was related to undergraduates feeling more supported. Findings support campus group exercise programs as opportunities to create reciprocal supportive ties for college students. Future research could further explore ways exercise and social support, particularly in group settings, affect health and well-being.

Assessment of university policies for service animals and emotional support animals.

OBJECTIVE: Assess administrative responsibilities and experiential effects of emotional support animal (ESA) and service animal (SA) policies on college campuses. PARTICIPANTS: Students at two four-year universities participated in an emotional support animals and service animals survey. Selected students and professional personnel participated in interviews and focus groups. METHODS: This mixed-methods study included quantitative survey data from 1,363 students, qualitative individual interviews (3) and a focus group (1) regarding emotional support animal (ESA) and service animal (SA). RESULTS: Seventy-one students reported having ESAs, 18 had SAs. Barriers for ESAs on campus included no ESAs outside of dorms, while SA-owners reported fewer barriers. University administrators followed federal guidelines for SAs but lacked clear guidelines for ESAs. Qualitative themes included lack of awareness, education, support for SA, and ESA accommodations. CONCLUSIONS: ESA and SA accommodations continue to rise, on university campuses. Clear guidelines and implementation processes are imperative for future improvements.

Egocentric network composition and structure relative to violence victimization among a sample of college students.

ObjectiveTo use egocentric network analysis to understand how composition and structure of egonetworks relate to violence victimization among college students. Participants: 697 students from a large southeastern university completed online surveys. Methods: Hierarchical logistic regression analyses assessed the relationship between egocentric network variables and a history of violence victimization. Results: Being connected to others with a history of violence victimization increased a student's odds of indicating their own history of physical, emotional, and sexual violence victimization. Having less dense egonetworks was related to sexual violence victimization, while being connected to less people of the same gender was related to emotional violence victimization. Conclusion: The way college students' networks are composed and structured could help in understanding violence victimization in this population, and should be considered in prevention and reactionary efforts on campuses. These findings add to the current literature largely focused on individual-level risk factors related to violence.

Social networks, group exercise, and anxiety among college students.

OBJECTIVE: This study aimed to evaluate the relationship between group exercise membership, social network characteristics, and general state anxiety in a sample of college students. Participants: 490 undergraduates from a private university in the southern US participated in the study. Methods: An egocentric network analysis was conducted to test whether demographic variables, leisure-time physical activity, group exercise membership, flourishing scores, and network variables were related to anxiety. Results: Regression analyses (R2 = .174, F = 7.650, p < .0001) suggest group exercise membership (ß = -.105, p = .034) and flourishing scores (ß = -.342, p < .0001) were related to lower anxiety scores, while being a racial/ethnic minority (ß = .094, p = .036), and having personal networks composed of more people who exercise often (ß = .100, p = .025), were related to higher anxiety scores in this sample. Conclusions: Findings suggest a connection between group exercise membership, activity habits of peers, and anxiety. Encouraging group exercise participation could be an effective way of combating anxiety for college students.

The use of magnetic field effects on photosensitizer luminescence as a novel probe for optical monitoring of oxygen in photodynamic therapy.

The effect of a magnetic field on the steady-state and time-resolved optical emission of a custom fullerene-linked photosensitizer (PS) in liposome cell phantoms was studied at various oxygen concentrations (0.19-190 microM). Zeeman splitting of the triplet state and hyperfine coupling, which control intersystem crossing between singlet and triplet states, are altered in the presence of low magnetic fields (B < 320 mT), perturbing the luminescence intensity and lifetime as compared to the triplet state at B = 0. Measurements of the luminescence intensity and lifetime were performed using a time-domain apparatus integrated with a magnet. We propose that by probing magnet-affected optical emissions, one can monitor the state of oxygenation throughout the course of photodynamic therapy. Since the magnetic field effect (MFE) operates primarily by affecting the radical ion pairs related to type I photodynamic action, the enhancement or suppression of the MFE can be used as a measure of the dynamic equilibrium between the type I and II photodynamic pathways. The unique photo-initiated charge-transfer properties of the PS used in this study allow it to serve as both cytotoxic agent and oxygen probe that can provide in situ dosimetric information at close to real time.

Bioluminescence imaging of point sources implanted in small animals post mortem: evaluation of a method for estimating source strength and depth.

The performance of a simple approach for the in vivo reconstruction of bioluminescent point sources in small animals was evaluated. The method uses the diffusion approximation as a forward model of light propagation from a point source in a homogeneous tissue to find the source depth and power. The optical properties of the tissue are estimated from reflectance images obtained at the same location on the animal. It was possible to localize point sources implanted in mice, 2-8 mm deep, to within 1 mm. The same performance was achieved for sources implanted in rat abdomens when the effects of tissue surface curvature were eliminated. The source power was reconstructed within a factor of 2 of the true power for the given range of depths, even though the apparent brightness of the source varied by several orders of magnitude. The study also showed that reconstructions using optical properties measured in situ were superior to those based on data in the literature.

Quantification of bioluminescence images of point source objects using diffusion theory models.

A simple approach for estimating the location and power of a bioluminescent point source inside tissue is reported. The strategy consists of using a diffuse reflectance image at the emission wavelength to determine the optical properties of the tissue. Following this, bioluminescence images are modelled using a single point source and the optical properties from the reflectance image, and the depth and power are iteratively adjusted to find the best agreement with the experimental image. The forward models for light propagation are based on the diffusion approximation, with appropriate boundary conditions. The method was tested using Monte Carlo simulations, Intralipid tissue-simulating phantoms and ex vivo chicken muscle. Monte Carlo data showed that depth could be recovered within 6% for depth 4-12 mm, and the corresponding relative source power within 12%. In Intralipid, the depth could be estimated within 8% for depth 4-12 mm, and the relative source power, within 20%. For ex vivo tissue samples, source depths of 4.5 and 10 mm and their relative powers were correctly identified.

The effect of light fluence rate in photodynamic therapy of normal rat brain.

This paper reports the effect of incident light fluence rate on the depth to which necrotic lesions are produced by photodynamic therapy (PDT) in the brains of normal Fisher rats. The rats were injected intraperitoneally with Photofrin (12.5 mg kg-1) 48 h prior to PDT with a fixed incident fluence of 35 J cm-2. The treatment was performed at 10, 50, 100, and 200 mW cm-2 and also in a periodic manner (30 s "on" at 100 mW cm-2, 30 s "off"). The depth to which necrosis occurred was determined 24 h after treatment by microscopic examination of tissue sections. No differences were found in the depth to which necrosis was produced by any of the five irradiation schedules. This finding is discussed in the context of other published dose-rate experiments.

Changes in in vivo optical properties and light distributions in normal canine prostate during photodynamic therapy.

The optical absorption and transport scattering coefficients of normal prostate tissue have been measured in vivo in dogs. The measurements were made at 630 nm before and during treatment by Photofin photodynamic therapy using interstitial optical fiber fluence-rate detectors. Corresponding measurements were made ex vivo, at 1 week after treatment, in the contralateral lobe. The optical properties were derived by applying a diffusion theory model to the fluence rates measured at two different source-detector fiber distances. While the in vivo pretreatment and in vivo contralateral post-treatment absorption and scattering values are self-consistent and in agreement with published data, significant changes were observed in the light fluence rates, and hence in the derived optical properties, during light irradiation. The possible causes of such changes are considered, and the implications for light dosimetry in photodynamic therapy are discussed.

Experimental verification of the effect of refractive index mismatch on the light fluence in a turbid medium.

Diffusion theory is often used to model the transport of light within tissue. It can be used to calculate the light fluence rate in tissue, for example, during photodynamic therapy, or to measure the absorption and scattering properties of tissue. For both of these applications, the influence of the interface between the tissue and the exterior medium on the fluence rate inside the tissue must be known in order to make accurate calculations. We present an experimental investigation of the effect of the refractive index mismatch at the tissue interface on the internal light fluence rate and on the spatially resolved diffuse reflectance as the boundary conditions of the tissue/external medium are changed. The effects of changing the relative refractive index at the boundary are compared to predictions of diffusion theory. The effect of the refractive index mismatch is predicted correctly by diffusion theory.

Improved method for the design of tissue compensators.

A program, WBEAM, is described which calculates dose distributions in planes perpendicular to the beam axis, taking into account both field shape and patient contour. WBEAM can be used to design compensators which when placed in the beam will produce uniform dose distributions in the plane of calculation. The program was tested in three different situations: a 30 x 30 cm field with a flat contour, a "mantle" field with a flat contour, a "mantle" field with a human-like contour. The program performs as designed: the dose distributions are accurate, and the compensators flatten the radiation beams to the specified limits.

Characteristics of an 18 MV photon beam from a Therac 20 Medical Linear Accelerator.

The 18 MV photon beam characteristics of a Therac 20 Medical Linear Accelerator manufactured by Atomic Energy of Canada Ltd, are presented. Tissue phantom ratios (TRP's) and percent depth dose data are given; for a 10 x 10 cm field, the percent depth dose at a depth of 10 cm is 78.5 (SSD 100 cm). The relative dose factors (RDF'S) are given and are analyzed to elucidate the relative contributions from phantom scatter, collimator scatter, and backscatter from the top of the collimators into the monitor chambers. The effect of field size and depth on the penumbra is described. Crossplots of the beam at a depth of 5 cm indicate that the flattening filter could be improved; there are hot spots of 108% near the corners of 40 x 40 fields.

A diffusion theory model of spatially resolved, steady-state diffuse reflectance for the noninvasive determination of tissue optical properties in vivo.

A model based upon steady-state diffusion theory which describes the radial dependence of diffuse reflectance of light from tissues is developed. This model incorporates a photon dipole source in order to satisfy the tissue boundary conditions and is suitable for either refractive index matched or mismatched surfaces. The predictions of the model were compared with Monte Carlo simulations as well as experimental measurements made with tissue simulating phantoms. The model describes the reflectance data accurately to radial distances as small as 0.5 mm when compared to Monte Carlo simulations and agrees with experimental measurements to distances as small as 1 mm. A nonlinear least-squares fitting procedure has been used to determine the tissue optical properties from the radial reflectance data in both phantoms and tissues in vivo. The optical properties derived for the phantoms are within 5%-10% of those determined by other established techniques. The in vivo values are also consistent with those reported by other investigators.

Total attenuation coefficients and scattering phase functions of tissues and phantom materials at 633 nm.

Measurements have been made of the total attenuation coefficient sigma t and the scattering phase function, S(theta), of 632.8 nm of light for a number of animal model tissues, blood, and inert scattering and absorbing media. Polystyrene microspheres of known size and refractive index, for which sigma t and S(theta) can be calculated by Mie theory, were used to test the experimental methods. The purpose of the study was to define typical ranges for these optical properties of tissues, as a contribution to the development of experimental and theoretical methods of light dosimetry in tissue, particularly related to photodynamic therapy of solid tumors. The results demonstrate that, for the representative tissues studied, the total attenuation coefficients are of the order of 10-100 mm-1, and that the scattering is highly forward peaked, with average cosine of scatter in the range 0.6-0.97.

Frequency-domain near-infrared photo diffusion imaging: initial evaluation in multitarget tissuelike phantoms.

In this paper, an initial evaluation of our finite element based frequency-domain image reconstruction algorithm is performed for experiments where multiple millimeter-sized heterogeneities are embedded within a tissue-equivalent (optically) background medium having multicentimeter dimensions. The cases considered consist of several interesting geometry and optical property contrast combinations including (i) two different-sized targets with the same contrast at three different separation distances; (ii) two different-sized targets with different contrasts at two different separation distances; and (iii) three targets with the same and different sizes and contrasts, respectively. The reconstruction algorithm that has been used is an enhanced version of our originally developed regularized least squares approach that now includes total variation minimization, dual meshing, and spatial low-pass filtering. Quantitative measures of image quality including the size, location, and shape of the embedded heterogeneities along with errors in their recovered optical property values are presented. The results show that multiple targets can be clearly detected for all combinations of locations, sizes, and contrast levels considered, but the quantitative nature of this detection is influenced by these parameters.

In vivo tests of the concept of photodynamic threshold dose in normal rat liver photosensitized by aluminum chlorosulphonated phthalocyanine.

In its simplest form, the photodynamic therapy (PDT) threshold dose model states that tissue necrosis due to PDT will occur if the number of photons absorbed by the photosensitizer per unit volume of tissue exceeds a critical value. This threshold is given by the product of photon fluence, photosensitizer concentration and specific absorption coefficient. To test the validity of this concept for PDT of normal rat liver sensitized with aluminum chlorosulphonated phthalocyanine (AISPC), all three of these parameters were varied by changing the injected AISPC dose, the wavelength of excitation and the irradiation geometry. The extent of necrosis caused by the treatment was consistent with the threshold model, except when the concentration of AISPC in the liver exceeded 20 micrograms g-1. For this animal model, we estimate the threshold to be (3.8 +/- 0.2) x 10(19) photons cm-3.

Effects of light beam size on fluence distribution and depth of necrosis in superficially applied photodynamic therapy of normal rat brain.

The light fluence distributions of 632.8 nm light incident on the exposed surface of normal rat brain in vivo have been measured using an interstitial, stereotactically-mounted optical fiber detector with isotropic response. The dependence of the relative fluence rate on depth and the spatial distribution of fluence were compared for incident beam diameters of 3 and 5 mm. The fluence rate at depth of 1-6 mm along the optical axis within the brain tissue was approximately 70% greater for a 5 mm diameter beam than for a 3 mm beam, at the same incident fluence rate, although the plots of the relative fluence rate vs depth were parallel over the depth range 1-6 mm. The depths of necrosis resulting from photodynamic treatment of brain tissue using the photosensitizer Photofrin and irradiation by 632 nm light with 3 and 5 mm incident beams were also measured. The observed difference in necrosis depths was consistent with the measured difference in fluence. The importance of beam size in photodynamic treatment with small diameter incident light fields is discussed.

Accuracy of noninvasive in vivo measurements of photosensitizer uptake based on a diffusion model of reflectance spectroscopy.

This study compares the photosensitizer concentration measured noninvasively in vivo by diffuse reflectance spectroscopy with the results of postmortem tissue solubilization and fluorometric assay. The reflectance spectrometer consists of a fiber optic surface probe, spectrometer and charge-coupled device (CCD) array detector. The surface probe has eight detection fibers separated from the light source fiber by distances ranging from 0.85 to 10 mm. The imaging spectrometer disperses the light from each detector fiber onto the two-dimensional CCD array, while maintaining spatial separation of each individual spectrum. A single exposure of the CCD therefore captures the reflectance spectrum ar eight distances and over a range of 300 nm. From the spectra, the tissue's optical scattering and absorption coefficients are determined using a diffusion model of light propagation. Changes in the tissue absorption are used to estimate the photosensitizer concentration. Normal New Zealand White rabbits were injected with aluminum phthalocyanine tetrasulfonate (AlPcS4) and probe measurements made 24 h after injection on the dorsal skin, on muscle after surgically turning the skin back and on liver. For skin, the noninvasive estimate to proportional to the true concentration but low by a factor of 3. Based on Monte Carlo modeling of multilayered systems, this underestimate is attributed to the layered structure of the skin and nonuniform AlPcS4 distribution. A comparison of the noninvasive concentration estimates to the postmortem assay results finds good agreement for liver tissue even though application of the diffusion model is not strictly justified.