Current levels of gonorrhoea screening in MSM in Belgium may have little effect on prevalence: a modelling study.

There is considerable uncertainty as to the effectiveness of Neisseria gonorrhoeae (NG) screening in men who have sex with men. It is important to ensure that screening has benefits that outweigh the risks of increased antibiotics resistance. We develop a mathematical model to estimate the effectiveness of screening on prevalence. Separable Temporal Exponential family Random Graph Models are used to model the sexual relationships network, both with main and casual partners. Next, the transmission of Gonorrhoea is simulated on this network. The models are implemented using the R package 'statnet', which we adapted among other things to incorporate infection status at the pharynx, urethra and rectum separately and to distinguish between anal sex, oral sex and rimming. The different screening programmes compared are no screening, 3.5% of the population screened, 32% screened and 50% screened. The model simulates day-by-day evolution for 10 years of a population of 10 000. If half of the population would be screened, the prevalence in the pharynx decreases from 11.9% to 10.2%. We conclude that the limited impact of screening on NG prevalence may not outweigh the increased risk of antibiotic resistance.

The role of sexual networks in studies of how BV and STIs increase the risk of subsequent reinfection.

Prior studies have demonstrated that both bacterial vaginosis (BV) and sexually transmitted infections (STIs) are strong independent risk factors for subsequent STI. In observational studies of this biological enhancement (BE) hypothesis, it is important to adjust for the risk of STI exposure so that the independent effect of BE can be assessed. We sought to model if two markers of local sexual network (partner concurrency and cumulative number of STIs) represented residual confounding in the models of risk for subsequent infection in a study that screened 3620 women for STIs every 3 months for a year. Mixed-effects logistic regression was used to calculate the odds ratios for an incident diagnosis of Chlamydia trachomatis, Neisseria gonorrhoeae, Trichomonas vaginalis and BV following a diagnosis of any of these four at the prior visit, controlling for the cumulative number of STIs and partner concurrency variables. We found that partner concurrency and cumulative number of STIs were each associated with incident infection, and in general, controlling for these variables reduced the strength of the association between prior and incident infections. We conclude that the frequently found association between prior and incident STIs is associated with both BE and sexual network structure.

Did AIDS mortality decrease the number of lifetime sexual partners in Kenya: an ecological analysis?

We assessed if there has been a decline in the median number of reported lifetime sexual partners in Kenya following the AIDS epidemic. The Wilcoxon rank-sum test was used to compare the median and interquartile range (IQR) of the number of lifetime sexual partners for men aged 20-54 years in the 1993 and 2008 Kenyan Demographic Health Surveys. The median number of sexual partners in 1993 increased rapidly to 10 partners reported at age 30 years then plateaued at this level. In 2008, the median number of sexual partners plateaued at around half the value of the 1993 plateau. The median number of lifetime sexual partners for men aged 20-54 years declined from 10 (IQR 4-20) in 1993 to 3 (IQR 2-7) in 2008 (P < 0·001). This decline could be due to a combination of the effects of AIDS mortality and a misreporting bias.

First-line tuberculosis treatment with double-dose rifampicin is well tolerated.

OBJECTIVE: To compare the occurrence of unfavourable treatment and safety outcomes of double-dose rifampicin (RMP; 20 mg/kg/d, intervention) with standard dose (10 mg/kg/d, control) in a first-line tuberculosis (TB) treatment regimen for smear-positive TB patients in Bangladesh.DESIGN: This was a randomised clinical trial. The primary efficacy and safety endpoints were the occurrence of an unfavourable treatment outcome (death, failure, relapse or loss to follow-up) and the occurrence of any serious drug-related adverse event (SAE).RESULTS: In primary efficacy analysis, among 343 control and 347 intervention patients, respectively 15.5% and 11.8% had an unfavourable outcome. In safety analysis, among 349 intervention and 352 control patients, respectively 4.3% and 2.6% experienced an SAE. These differences were not significant. There was a significantly lower occurrence of SAEs, explained by a lower occurrence of hepatic toxicity, in a RMP double-dosed but erroneously HZE (isoniazid+pyrazinamide+ethambutol) under-dosed subgroup.CONCLUSIONS: Our findings show that there is no statistically significant difference in terms of efficacy and safety between standard and double-dose RMP. An accidental finding (related to dosage levels of the standard regimen) suggests that high-dose RMP is potentially a lesser cause of hepatotoxicity. Larger trials with more power, or trials with at least a triple-dose might be needed to clearly see the effect of high-dose RMP on unfavourable outcomes.

Is frontloaded sputum microscopy an option in active tuberculosis case finding?

SETTING: Active tuberculosis (TB) case finding (ACF) in Phnom Penh, Cambodia using light-emitting diode fluorescence microscopy (FM). OBJECTIVE: To evaluate the smear-positive yield of frontloaded (same-day) smear microscopy in ACF. DESIGN: All presumptive TB cases screened through ACF were asked to provide three sputum specimens: two spot specimens on Day 1 and a morning specimen on Day 2 (spot-spot-morning, SSM). Laboratory technicians blinded to previous results read the smears using FM. We considered only SSM series with at least one positive smear to calculate the proportion of TB cases missed and to determine the difference between the spot-spot (SS) and spot-morning (SM) approach. RESULTS: Of 4616 presumptive TB patients enrolled, 3306 provided three sputum samples. Of 2957 (89.4%) who followed the SSM approach, 188 (6.4%) were smear-positive: 177 on SM and 160 on SS. The incremental yield of the second sputum sample was 18.1% for SM vs. 9.4% for SS. Relative to any smear-positive case detected by SSM, 28/188 (14.9%, 95%CI 10.1-20.8) TB cases would be missed by SS vs. 11/188 (5.9%, 95%CI 3.0-10.2) by SM. The difference in the proportion of missed TB patients was 9.0% (P = 0.006). CONCLUSION: ACF frontloaded sputum microscopy is inferior in terms of smear-positive yield: the SS approach would have missed a significant proportion of smear-positive TB.

A comparison of macroscopic lipid content within porcine pulmonary and aortic valves. Implications for bioprosthetic valves.

Lipid droplets have been demonstrated within both explanted porcine bioprostheses and normal porcine aortic valves. Because of the increasing interest in pulmonary valves as an allograft or xenograft aortic valve substitute, we examined the incidence and distribution of such lipid deposits in 50 porcine aortic valves and 50 matched porcine pulmonary valves. All 300 cusps were removed with surgical scissors and, under a dissecting microscope, the ventricularis layer was removed to expose the spongiosal layer. Macroscopic extracellular lipid droplets analyzed by means of a dissecting microscope with an eyepiece grid and stereology point-counting techniques to provide an area-density average spatial probability map for each cusp. Only 8% of porcine aortic valves were free of lipid, with the distribution of the lipids being 52% +/- 14% right coronary cusp, 90% +/- 8% left coronary cusp, and 68% +/- 13% noncoronary cusp. Of the pulmonary valves, 60% were free of lipid, with the incidence of lipids being 26% +/- 12% left cusp, 6% +/- 7% right cusp, and 12% +/- 9% anterior cusp. Subsequently, lipid cluster samples underwent thin-layer chromatography, which showed them to be phospholipids, oleic acid (fatty acid), triglycerides, and unesterified cholesterol. One primary mode of bioprosthetic valve failure is leaflet calcification. The similarity of distribution within the spongiosal layer between leaflet calcification and intrinsic cusp lipids suggests that the observed lipids might act as a nucleation site for calcification. The substantially lower incidence of lipid in pulmonary valves therefore may represent a potential benefit when these valves are considered for use as aortic valve replacements.

Enhanced detection of cardiac myocyte damage by polarized light microscopy. Use in a model of coxsackievirus B3-induced myocarditis.

Although accurate detection of cardiac muscle damage is critical in the diagnosis of acute myocarditis or acute cellular rejection in both clinical and experimental settings, the histologic evaluation is frequently uncertain without specialized stains. In a study of adult male A/J mice infected with 2x10(5) plaque-forming units of myocarditic coxsackievirus B3, cardiac muscle injury causing myofibrillar disruption was detected as a loss of muscle birefringence by polarized light microscopy. The technique was corroborated by comparison with Masson's trichrome stain and was helpful for histologic examination especially at the early preinflammatory stages of lesion development or in fringe territories of focal lesions. Polarized light microscopy is thus an available means to enhance the histologic determination of cardiac myocyte damage and has specific advantage in an absence of specialized stains.

A real vessel phantom for imaging experimentation.

Vascular phantoms are used to evaluate imaging techniques such as ultrasound (US), CT, and angiography. They are expected to mimic the vasculature, surrounding tissue, and blood, and therefore must meet specific requirements on the mimicking materials, with respect to x-ray attenuation and acoustic properties (velocity, attenuation). In the past, researchers have used a variety of vessel models, including walled (typically latex tube) and wall-less phantoms (obtained by moulding a lumen in a block of agar). These models lacked the exact geometry of human vessels as well as pathologic features such as plaques and calcifications. To overcome these disadvantages, this paper describes a real vessel phantom for US and x-ray studies. The phantom consists of an agar-filled acrylic box containing a formaldehyde fixed section of a real human vessel (obtained at autopsy) cannulated onto two acrylic tubes. This phantom was evaluated by comparing the images obtained with x-ray angiography, CT, and 3-D B-mode US. The images show good overall correlation based on the location of the geometrical features within the phantom, such as lumen, plaques, and calcifications. Discrepancies, artifacts, and difficulties were minor, and are discussed. The use of a real vessel, with its natural geometry and pathology, makes this phantom attractive for evaluation of imaging techniques including projection radiography, CT and US, and for extending its use to MR and US based flow studies.

Laser-induced fluorescence (LIF) recognition of the structural composition of porcine heart valves.

Reconstruction and replacement of heart valves with grafts fro pig tissue is a common procedure. However, bioprosthetic valves wear out in a shorter time span than mechanical valves. Bioprosthetic valve structure may contribute to degenerative changes that lead to valve failure. There is, at present, no method to examine the structure of a tissue valve prior to implant. Laser-induced fluorescence (LIF) of natural fluorophores is an elegant method developed for the detection of tumors, dermal lesions and atherosclerosis. We have studied LIF as a potential diagnostic technique for analysis of valvular tissue. Using excimer laser excitation, we examined natural fluorescence recorded from porcine aortic, mitral and pulmonary valves. All three valve outflow surface tissue layers are less fluorescent at 390-450 nm than the inflow layers. Immunohistochemical analysis of collagen I and elastin content in inflow and outflow surface layers of all three valves correlated well with LIF intensities and dI/d lambda values at selected wavelengths. In conclusion, the differences observed in emitted LIF from valve surface layers are found to correlate well with diversity in the structural protein content. The LIF spectroscopic measurements may provide an appropriate tool for examination of tissue valve structure prior to use for implantation.

The pericardial bioprosthesis: altered tissue shear properties following glutaraldehyde fixation.

BACKGROUND AND AIM OF THE STUDY: Glutaraldehyde-fixed bovine pericardial tissue used in the construction of valvular bioprostheses undergoes repeated bending stress during the cardiac cycle. To bend smoothly, internal tissue shearing is required. The effect of glutaraldehyde fixation on internal shear properties of this material was examined. METHODS: Pericardium from each of 12 bovine hearts was cut into two pieces; one piece was retained as fresh tissue, the other was glutaraldehyde-fixed. Circular samples were then mounted and installed in a shear testing apparatus. For each sample, the shear stress versus shear strain characteristics were measured in circumferential and radial directions at strain rates of 1.0, 0.1 and 0.02 s(-1) while immersed in a 20 degrees C bath; similar measurements were made on six fresh and six fixed samples at 37 degrees C. In addition, the stress relaxation properties were measured by holding the tissue at maximum shear for 100 s after each of the three shear deformations, and recording force generated with time. RESULTS: The shear stress-strain test on fresh tissue (n = 12) showed non-linear behavior at the three shear rates. The shear modulus for fresh tissue increased from <1.0 kPa to 5 kPa at a shear strain approaching 1.0, and results were identical in radial or circumferential directions. For glutaraldehyde-fixed pericardium (n = 12), shear modulus increased promptly to 15-20 kPa at a strain of 0.2, and did not vary with strain rate. Shear relaxation was similar in fresh and fixed tissue. CONCLUSION: Fresh pericardium sheared easily at low shear stresses, with minimal resistance developing until the shear strain exceeded 0.5, while glutaraldehyde-fixed tissue displayed a marked resistance to shearing, with an immediate rise in shear stress at low strain. No differences were detected in shear properties between radial and circumferential directions. Such marked tissue stiffening may be a factor in collagen fiber disruption, leading to bioprosthetic heart valve failure.

A real vessel phantom for flow imaging: 3-D Doppler ultrasound of steady flow.

Vascular phantoms are used to assess the capabilities of various imaging techniques, such as x-ray CT and angiography, and B-mode, power Doppler, and colour Doppler ultrasound (US). They should, therefore, accurately mimic the vasculature, blood, and surrounding tissue, in regard to both imaging properties and vessel geometry. In the past, a variety of walled and wall-less vessel models have been used. However, these models only approximate the true vessel geometry, and generally lack pathologic features such as plaques or calcifications. To amend these deficiencies, we have developed a real vessel phantom for US and x-ray studies, which comprises a fixed human vessel specimen, cannulated onto two acrylic tubes, and embedded in agar in an acrylic box. Earlier, we demonstrated a good overall correlation between x-ray angiography, CT, and 3-D B-mode US images of this phantom. Here, we extend its use to flow imaging with 3-D power and 3-D colour Doppler US.

The radiographic quantitation of aortic valve calcification: implications for assessing bioprosthetic valve calcification in vitro.

Calcification of natural aortic and bioprosthetic heart valves is a poorly understood phenomenon that results in valvular obstruction and tissue failure. We describe a non-destructive quantitative computed microtomographic (QCT) technique for determining both calcium content and local calcium distribution within explanted valves. As a reference standard, a dual-energy x-ray absorptiometry (DEXA) system with an accuracy demonstrated to be within 1% of the true calcium mass of test material was used to obtain the total calcium content of 24 human aortic valve cusps recovered at autopsy from patients aged 51-80 years. These cusps were then scanned using our unique volume QCT scanner, with multiple x-ray projections acquired by rotating the explanted tissue through a single axis of rotation. A three-dimensional cross-sectional map was reconstructed for each cusp. Voxel size was 0.003 mm3 and a calibration phantom was used to calculate calcium content. The minimum detection limit for calcium mass was 1 mg within the whole cusp. The DEXA and QCT scans were compared with respect to total calcium content, which ranged from 0 to 15 mg. An excellent correlation between the two independent techniques was demonstrated with an r2 value of 0.94 (p < 0.001). Non-destructive microtomographic CT scanning provided excellent volumetric density measurements, with quantitative 3D images permitting an assessment of any individual area of the cusp for calcium content and spatial distribution. This new approach to valve tissue analysis allows for subsequent histologic assessment.

Classification of incidence and prevalence of certain sexually transmitted infections by world regions.

OBJECTIVES: This study sought to assess if there is a meaningful way in which variations in sexually transmitted infection (STI) prevalence can be classified at the level of world regions. METHODS: Linear regression was performed to assess if the incidence and prevalence of six STIs (HIV, herpes simplex virus type 2, chlamydia, gonorrhea, syphilis, and trichomoniasis) by world region was positively correlated. Partitioning around medoids (PAM) was then used to assess if the regions of the world can be classified according to the incidence and prevalence of these STIs. RESULTS: We found evidence that STI incidence/prevalence varies considerably in different regions around the world. Linear regression revealed that the incidence and prevalence of certain STIs by world region was positively correlated (Pearson's correlation coefficient varied from 0.664 to 0.985). PAM provided support for dividing the world regions into two, three, or four STI incidence/prevalence categories, but it provided most support for the two-category system. In each of these systems the East Asia/Pacific and North Africa/Middle East regions were in the lowest STI category and Sub-Saharan Africa was the only region in the high STI category. CONCLUSIONS: The incidence and prevalence of certain STIs by world region are positively correlated. The world regions can be meaningfully classified according to STI incidence/prevalence.