International Society of Urological Pathology (ISUP) Consensus Conference on Handling and Staging of Radical Prostatectomy Specimens. Working group 4: seminal vesicles and lymph nodes.

The 2009 International Society of Urological Pathology Consensus Conference in Boston made recommendations regarding the standardization of pathology reporting of radical prostatectomy specimens. Issues relating to the infiltration of tumor into the seminal vesicles and regional lymph nodes were coordinated by working group 4. There was a consensus that complete blocking of the seminal vesicles was not necessary, although sampling of the junction of the seminal vesicles and prostate was mandatory. There was consensus that sampling of the vas deferens margins was not obligatory. There was also consensus that muscular wall invasion of the extraprostatic seminal vesicle only should be regarded as seminal vesicle invasion. Categorization into types of seminal vesicle spread was agreed by consensus to be not necessary. For examination of lymph nodes, there was consensus that special techniques such as frozen sectioning were of use only in high-risk cases. There was no consensus on the optimal sampling method for pelvic lymph node dissection specimens, although there was consensus that all lymph nodes should be completely blocked as a minimum. There was also a consensus that a count of the number of lymph nodes harvested should be attempted. In view of recent evidence, there was consensus that the diameter of the largest lymph node metastasis should be measured. These consensus decisions will hopefully clarify the difficult areas of pathological assessment in radical prostatectomy evaluation and improve the concordance of research series to allow more accurate assessment of patient prognosis.

Combining clinical factors and quantitative ultrasound improves the detection of women both at low and high risk for hip fracture.

We hypothesized that combining clinical risk factors (CRF) with the heel stiffness index (SI) measured via quantitative ultrasound (QUS) would improve the detection of women both at low and high risk for hip fracture. Categorizing women by risk score improved the specificity of detection to 42.4%, versus 33.8% using CRF alone and 38.4% using the SI alone. This combined CRF-SI score could be used wherever and whenever DXA is not readily accessible. INTRODUCTION AND HYPOTHESIS: Several strategies have been proposed to identify women at high risk for osteoporosis-related fractures; we wanted to investigate whether combining clinical risk factors (CRF) and heel QUS parameters could provide a more accurate tool to identify women at both low and high risk for hip fracture than either CRF or QUS alone. METHODS: We pooled two Caucasian cohorts, EPIDOS and SEMOF, into a large database named "EPISEM", in which 12,064 women, 70 to 100 years old, were analyzed. Amongst all the CRF available in EPISEM, we used only the ones which were statistically significant in a Cox multivariate model. Then, we constructed a risk score, by combining the QUS-derived heel stiffness index (SI) and the following seven CRF: patient age, body mass index (BMI), fracture history, fall history, diabetes history, chair-test results, and past estrogen treatment. RESULTS: Using the composite SI-CRF score, 42% of the women who did not report a hip fracture were found to be at low risk at baseline, and 57% of those who subsequently sustained a fracture were at high risk. Using the SI alone, corresponding percentages were 38% and 52%; using CRF alone, 34% and 53%. The number of subjects in the intermediate group was reduced from 5,400 (including 112 hip fractures) and 5,032 (including 111 hip fractures) to 4,549 (including 100 including fractures) for the CRF and QUS alone versus the combination score. CONCLUSIONS: Combining clinical risk factors to heel bone ultrasound appears to correctly identify more women at low risk for hip fracture than either the stiffness index or the CRF alone; it improves the detection of women both at low and high risk.

Quantitative ultrasound in the management of osteoporosis: the 2007 ISCD Official Positions

Dual-energy X-ray absorptiometry (DXA) is commonly used in the care of patients for diagnostic classification of osteoporosis, low bone mass (osteopenia), or normal bone density; assessment of fracture risk; and monitoring changes in bone density over time. The development of other technologies for the evaluation of skeletal health has been associated with uncertainties regarding their applications in clinical practice. Quantitative ultrasound (QUS), a technology for measuring properties of bone at peripheral skeletal sites, is more portable and less expensive than DXA, without the use of ionizing radiation. The proliferation of QUS devices that are technologically diverse, measuring and reporting variable bone parameters in different ways, examining different skeletal sites, and having differing levels of validating data for association with DXA-measured bone density and fracture risk, has created many challenges in applying QUS for use in clinical practice. The International Society for Clinical Densitometry (ISCD) 2007 Position Development Conference (PDC) addressed clinical applications of QUS for fracture risk assessment, diagnosis of osteoporosis, treatment initiation, monitoring of treatment, and quality assurance/quality control. The ISCD Official Positions on QUS resulting from this PDC, the rationale for their establishment, and recommendations for further study are presented here.

How can continuing professional development better promote shared decision-making? Perspectives from an international collaboration.

ABSTRACT: BACKGROUND: Shared decision-making is not widely implemented in healthcare. We aimed to set a research agenda about promoting shared decision-making through continuing professional development. METHODS: Thirty-six participants met for two days. RESULTS: Participants suggested ways to improve an environmental scan that had inventoried 53 shared decision-making training programs from 14 countries. Their proposed research agenda included reaching an international consensus on shared decision-making competencies and creating a framework for accrediting continuing professional development initiatives in shared decision-making. CONCLUSIONS: Variability in shared decision-making training programs showcases the need for quality assurance frameworks.

Evaluation des technologies médicales : travaux présentés pendant le Congrès TEKMED 87 = Assessment of medical technologies : the papers presented during the TEKMED 87 Congress

[Table des matières] Technology assessment in health care in the United States: an historical review / S. Perry. - The aims and methods of technology assessment / JH Glasser. - Evaluation des technologies de la santé / A. Griffiths. - Les données nécessaires pour l'évaluation des technologies médicales / R. Chrzanowski, F. Gutzwiller, F. Paccaud. - Economic issues in technology assessment/DR Lairson, JM Swint. - Two decades of experience in technology assessment: evaluating the safety, performance, and cost effectiveness of medical equipment / JJ Nobel. - Demography and technology assessment / H. Hansluwka. - Méthodes expérimentale et non expérimentale pour l'évaluation des innovations technologiques / R. Chrzanowski, F. Paccaud. - Skull radiography in head trauma: a successful case of technology assessment / NT Racoveanu. - Complications associées à l'anesthésie: une étude prospective en France / L. Tiret et al. - Impact de l'information publique sur les taux opératoires: le cas de l'hystérectomie / G. Domenighetti, P. Luraschi, A. Casabianca. - The clinical effectiveness of acupuncture for the relief of chronic pain / MS Patel, F. Gutzwiller, F. Paccaud, A. Marazzi. - Soins à domicile et hébergement à long terme: à la recherche d'un développement optimum / G. Tinturier. - Economic evaluation of six scenarios for the treatment of stones in the kidney and ureter by surgery or ESWL / MS Patel et al. - Technology assessment and medical practice / F. Gutzwiller. - Technology assessment and health policy / SJ Reiser. - Global programme on appropriate technology for health, its role and place within WHO / K. Staehr Johansen.

Prognostic value of early MR imaging in term infants with severe perinatal asphyxia.

The prognostic significance of magnetic resonance imaging (MRI) in the neonatal period was studied prospectively in 43 term infants with perinatal asphyxia. MRI was performed between 1 and 14 days after birth with a high field system (2.35 Tesla). Neurodevelopmental outcome was assessed by a standardized neurological examination and the Griffiths developmental test at a mean age of 18.9 months. The predictive value of the various MRI patterns was as follows: Severe diffuse brain injury (pattern AII+III; n = 7) and lesions of thalamus and basal ganglia (pattern C; n = 5) were strongly associated with poor outcome and greatly reduced head growth. Mild diffuse brain injury (pattern AI; n = 7), parasagittal lesions (B; n = 7), periventricular hyperintensity (D; n = 2), focal brain necrosis and hemorrhage (E; n = 3) and periventricular hypointense stripes (on T2-weighted images; F; n = 3) led in one third of the infants to minor neurological disturbances and mild developmental delay. Infants with normal MRI findings (G; n = 9) developed normally with the exception of one infant who was mildly delayed at 18 months. The results indicate that MRI examination during the first two weeks of life is of prognostic significance in term infants suffering from perinatal asphyxia. Severe hypoxic-ischemic brain lesions were associated highly significantly with poor neuro-developmental outcome, whereas infants with inconspicuous MRI developed normally.

Defining risk thresholds for a 10-year probability of hip fracture model that combines clinical risk factors and quantitative ultrasound: results using the EPISEM cohort.

Using a large prospective cohort of over 12,000 women, we determined 2 thresholds (high risk and low risk of hip fracture) to use in a 10-yr hip fracture probability model that we had previously described, a model combining the heel stiffness index measured by quantitative ultrasound (QUS) and a set of easily determined clinical risk factors (CRFs). The model identified a higher percentage of women with fractures as high risk than a previously reported risk score that combined QUS and CRF. In addition, it categorized women in a way that was quite consistent with the categorization that occurred using dual X-ray absorptiometry (DXA) and the World Health Organization (WHO) classification system; the 2 methods identified similar percentages of women with and without fractures in each of their 3 categories, but the 2 identified only in part the same women. Nevertheless, combining our composite probability model with DXA in a case findings strategy will likely further improve the detection of women at high risk of fragility hip fracture. We conclude that the currently proposed model may be of some use as an alternative to the WHO classification criteria for osteoporosis, at least when access to DXA is limited.

Real-time quantitative PCR assay for measurement of bird telomeres

We present the application of a real-time quantitative PCR assay, previously developed to measure relative telomere length in humans and mice, to two bird species, the zebra finch Taeniopygia guttata and the Alpine swift Apus melba. This technique is based on the PCR amplification of telomeric (TTAGGG)(n) sequences using specific oligonucleotide primers. Relative telomere length is expressed as the ratio (T/S) of telomere repeat copy number (T) to control single gene copy number (S). This method is particularly useful for comparisons of individuals within species, or where the same individuals are followed longitudinally. We used glyceraldehyde-3-phosphate dehydrogenase (GAPDH) as a single control gene. In both species, we validated our PCR measurements of relative telomere length against absolute measurements of telomere length determined by the conventional method of quantifying telomere terminal restriction fragment (TRF) lengths using both the traditional Southern blot analysis (Alpine swifts) and in gel hybridization (zebra finches). As found in humans and mice, telomere lengths in the same sample measured by TRF and PCR were well correlated in both the Alpine swift and the zebra finch.. Hence, this PCR assay for measurement of bird telomeres, which is fast and requires only small amounts of genomic DNA, should open new avenues in the study of environmental factors influencing variation in telomere length, and how this variation translates into variation in cellular and whole organism senescence.

Meta-analysis and imputation refines the association of 15q25 with smoking quantity.

Smoking is a leading global cause of disease and mortality. We established the Oxford-GlaxoSmithKline study (Ox-GSK) to perform a genome-wide meta-analysis of SNP association with smoking-related behavioral traits. Our final data set included 41,150 individuals drawn from 20 disease, population and control cohorts. Our analysis confirmed an effect on smoking quantity at a locus on 15q25 (P = 9.45 x 10(-19)) that includes CHRNA5, CHRNA3 and CHRNB4, three genes encoding neuronal nicotinic acetylcholine receptor subunits. We used data from the 1000 Genomes project to investigate the region using imputation, which allowed for analysis of virtually all common SNPs in the region and offered a fivefold increase in marker density over HapMap2 (ref. 2) as an imputation reference panel. Our fine-mapping approach identified a SNP showing the highest significance, rs55853698, located within the promoter region of CHRNA5. Conditional analysis also identified a secondary locus (rs6495308) in CHRNA3.

La sélection intra-universitaire : un bon ou mauvais moyen d'identifier les meilleurs étudiants en médecine ?

Résumé: La sélection des étudiants en médecine se fait à la Faculté de Médecine de Lausanne pendant les deux premières années du curriculum, sur la base d'examens portant sur les sciences de base. Le risque est par ce biais de privilégier le passage dans les années cliniques d'étudiants doués sur le plan scientifique, mais ne possédant pas nécessairement les qualités humaines que devrait avoir un bon médecin. La présente étude a porté sur une volée d'étudiants (n = 115) ayant réussi la première partie de l'examen final à la fin de la troisième année des études de médecine. A cette occasion les étudiants ont passé un examen oral de médecine psycho-sociale permettant d'évaluer leurs aptitudes à gérer la relation médecin- malade. Les notes obtenues à cet examen ont été mises en rapport avec celles obtenues en première année lors d'un examen écrit de physique et de physiologie. Les résultats ont montré que la performance à ces disciplines de base n'ont pas de valeur prédictive quant aux performances futures à l'examen de médecine psycho-sociale. Par ailleurs il est apparu que le type de maturité acquis pendant le gymnase n'a pas d'influence majeure sur la progression des étudiants pendant les années pré-cliniques des études de médecine.

Assessment of the 10-year probability of osteoporotic hip fracture combining clinical risk factors and heel bone ultrasound: the EPISEM prospective cohort of 12,958 elderly women.

This study aimed to develop a hip screening tool that combines relevant clinical risk factors (CRFs) and quantitative ultrasound (QUS) at the heel to determine the 10-yr probability of hip fractures in elderly women. The EPISEM database, comprised of approximately 13,000 women 70 yr of age, was derived from two population-based white European cohorts in France and Switzerland. All women had baseline data on CRFs and a baseline measurement of the stiffness index (SI) derived from QUS at the heel. Women were followed prospectively to identify incident fractures. Multivariate analysis was performed to determine the CRFs that contributed significantly to hip fracture risk, and these were used to generate a CRF score. Gradients of risk (GR; RR/SD change) and areas under receiver operating characteristic curves (AUC) were calculated for the CRF score, SI, and a score combining both. The 10-yr probability of hip fracture was computed for the combined model. Three hundred seven hip fractures were observed over a mean follow-up of 3.2 yr. In addition to SI, significant CRFs for hip fracture were body mass index (BMI), history of fracture, an impaired chair test, history of a recent fall, current cigarette smoking, and diabetes mellitus. The average GR for hip fracture was 2.10 per SD with the combined SI + CRF score compared with a GR of 1.77 with SI alone and of 1.52 with the CRF score alone. Thus, the use of CRFs enhanced the predictive value of SI alone. For example, in a woman 80 yr of age, the presence of two to four CRFs increased the probability of hip fracture from 16.9% to 26.6% and from 52.6% to 70.5% for SI Z-scores of +2 and -3, respectively. The combined use of CRFs and QUS SI is a promising tool to assess hip fracture probability in elderly women, especially when access to DXA is limited.

Directional dominance on stature and cognition in diverse human populations.

Homozygosity has long been associated with rare, often devastating, Mendelian disorders, and Darwin was one of the first to recognize that inbreeding reduces evolutionary fitness. However, the effect of the more distant parental relatedness that is common in modern human populations is less well understood. Genomic data now allow us to investigate the effects of homozygosity on traits of public health importance by observing contiguous homozygous segments (runs of homozygosity), which are inferred to be homozygous along their complete length. Given the low levels of genome-wide homozygosity prevalent in most human populations, information is required on very large numbers of people to provide sufficient power. Here we use runs of homozygosity to study 16 health-related quantitative traits in 354,224 individuals from 102 cohorts, and find statistically significant associations between summed runs of homozygosity and four complex traits: height, forced expiratory lung volume in one second, general cognitive ability and educational attainment (P < 1 × 10(-300), 2.1 × 10(-6), 2.5 × 10(-10) and 1.8 × 10(-10), respectively). In each case, increased homozygosity was associated with decreased trait value, equivalent to the offspring of first cousins being 1.2 cm shorter and having 10 months' less education. Similar effect sizes were found across four continental groups and populations with different degrees of genome-wide homozygosity, providing evidence that homozygosity, rather than confounding, directly contributes to phenotypic variance. Contrary to earlier reports in substantially smaller samples, no evidence was seen of an influence of genome-wide homozygosity on blood pressure and low density lipoprotein cholesterol, or ten other cardio-metabolic traits. Since directional dominance is predicted for traits under directional evolutionary selection, this study provides evidence that increased stature and cognitive function have been positively selected in human evolution, whereas many important risk factors for late-onset complex diseases may not have been.

Robust Estimates of the Negative Binomial Model

We consider robust parametric procedures for univariate discrete distributions, focusing on the negative binomial model. The procedures are based on three steps: ?First, a very robust, but possibly inefficient, estimate of the model parameters is computed. ?Second, this initial model is used to identify outliers, which are then removed from the sample. ?Third, a corrected maximum likelihood estimator is computed with the remaining observations. The final estimate inherits the breakdown point (bdp) of the initial one and its efficiency can be significantly higher. Analogous procedures were proposed in [1], [2], [5] for the continuous case. A comparison of the asymptotic bias of various estimates under point contamination points out the minimum Neyman's chi-squared disparity estimate as a good choice for the initial step. Various minimum disparity estimators were explored by Lindsay [4], who showed that the minimum Neyman's chi-squared estimate has a 50% bdp under point contamination; in addition, it is asymptotically fully efficient at the model. However, the finite sample efficiency of this estimate under the uncontaminated negative binomial model is usually much lower than 100% and the bias can be strong. We show that its performance can then be greatly improved using the three step procedure outlined above. In addition, we compare the final estimate with the procedure described in