The AO comprehensive classification of pediatric long-bone fractures: a web-based multicenter agreement study.

The first AO comprehensive pediatric long-bone fracture classification system has been proposed following a structured path of development and validation with experienced pediatric surgeons. A Web-based multicenter agreement study involving 70 surgeons in 15 clinics and 5 countries was conducted to assess the reliability and accuracy of this classification when used by a wide range of surgeons with various levels of experience. Training was provided at each clinic before the session. Using the Internet, participants could log in at any time and classify 275 supracondylar, radius, and tibia fractures at their own pace. The fracture diagnosis was made following the hierarchy of the classification system using both clinical terminology and codes. kappa coefficients for the single-surgeon diagnosis of epiphyseal, metaphyseal, or diaphyseal fracture type were 0.66, 0.80, and 0.91, respectively. Median accuracy estimates for each bone and type were all greater than 80%. Depending on their experience and specialization, surgeons greatly varied in their ability to classify fractures. Pediatric training and at least 2 years of experience were associated with significant improvement in reliability and accuracy. Kappa coefficients for diagnosis of specific child patterns were 0.51, 0.63, and 0.48 for epiphyseal, metaphyseal, and diaphyseal fractures, respectively. Identified reasons for coding discrepancies were related to different understandings of terminology and definitions, as well as poor quality radiographic images. Results supported some minor adjustments in the coding of fracture type and child patterns. This classification system received wide acceptance and support among the surgeons involved. As long as appropriate training could be performed, the system classification was reliable, especially among surgeons with a minimum of 2 years of clinical experience. We encourage broad-based consultation between surgeons' international societies and the use of this classification system in the context of clinical practice as well as prospectively for clinical studies.

Condom use with steady partners among heterosexual people living with HIV in Europe: testing the information-motivation-behavioral skills model.

Guided by a modified information-motivation-behavioral skills model, this study identified predictors of condom use among heterosexual people living with HIV with their steady partners. Consecutive patients at 14 European HIV outpatient clinics received an anonymous, standardized, self-administered questionnaire between March and December 2007. Data were analyzed using descriptive statistics and two-step backward elimination regression analyses stratified by gender. The survey included 651 participants (n = 364, 56% women; n = 287, 44%). Mean age was 39 years for women and 43 years for men. Most had acquired HIV sexually and more than half were in a serodiscordant relationship. Sixty-three percent (n = 229) of women and 59% of men (n = 169) reported at least one sexual encounter with a steady partner 6 months prior to the survey. Fifty-one percent (n = 116) of women and 59% of men (n = 99) used condoms consistently with that partner. In both genders, condom use was positively associated with subjective norm conducive to condom use, and self-efficacy to use condoms. Having a partner whose HIV status was positive or unknown reduced condom use. In men, higher education and knowledge about condom use additionally increased condom use, while the use of erectile-enhancing medication decreased it. For women, HIV disclosure to partners additionally reduced the likelihood of condom use. Positive attitudes to condom use and subjective norm increased self-efficacy in both genders, however, a number of gender-related differences appeared to influence self-efficacy. Service providers should pay attention to the identified predictors of condom use and adopt comprehensive and gender-related approaches for preventive interventions with people living with HIV.

Testing new identity models and processes in French-speaking adolescents and emerging adults students

Developing a sense of identity is a crucial psychosocial task for young people. The purpose of this study was to evaluate identity development in French-speaking adolescents and emerging adults (in France and Switzerland) using a process-oriented model of identity formation including five dimensions (i.e., exploration in breadth, commitment making, exploration in depth, identification with commitment, and ruminative exploration). The study included participants from three different samples (total N = 2239, 66.7% women): two samples of emerging adult student and one sample of adolescents. Results confirmed the hypothesized five-factor dimensional model of identity in our three samples and provided evidence for convergent validity of the model. The results also indicated that exploration in depth might be subdivided in two aspects: a first form of exploration in depth leading to a better understanding and to an increase of the strength of current commitments and a second form of exploration in depth leading to a re-evaluation and a reconsideration of current commitments. Further, the identity status cluster solution that emerged is globally in line with previous literature (i.e., achievement, foreclosure, moratorium, carefree diffusion, diffused diffusion, undifferentiated). However, despite a structural similarity, we found variations in identity profiles because identity development is shaped by cultural context. These specific variations are discussed in light of social, educational and economic differences between France and the French-speaking part of Switzerland. Implications and suggestions for future research are offered.

Limited clinical benefit of minority K103N and Y181C-variant detection in addition to routine genotypic resistance testing in antiretroviral therapy-naive patients.

OBJECTIVE: The presence of minority nonnucleoside reverse transcriptase inhibitor (NNRTI)-resistant HIV-1 variants prior to antiretroviral therapy (ART) has been linked to virologic failure in treatment-naive patients. DESIGN: We performed a large retrospective study to determine the number of treatment failures that could have been prevented by implementing minority drug-resistant HIV-1 variant analyses in ART-naïve patients in whom no NNRTI resistance mutations were detected by routine resistance testing. METHODS: Of 1608 patients in the Swiss HIV Cohort Study, who have initiated first-line ART with two nucleoside reverse transcriptase inhibitors (NRTIs) and one NNRTI before July 2008, 519 patients were eligible by means of HIV-1 subtype, viral load and sample availability. Key NNRTI drug resistance mutations K103N and Y181C were measured by allele-specific PCR in 208 of 519 randomly chosen patients. RESULTS: Minority K103N and Y181C drug resistance mutations were detected in five out of 190 (2.6%) and 10 out of 201 (5%) patients, respectively. Focusing on 183 patients for whom virologic success or failure could be examined, virologic failure occurred in seven out of 183 (3.8%) patients; minority K103N and/or Y181C variants were present prior to ART initiation in only two of those patients. The NNRTI-containing, first-line ART was effective in 10 patients with preexisting minority NNRTI-resistant HIV-1 variant. CONCLUSION: As revealed in settings of case-control studies, minority NNRTI-resistant HIV-1 variants can have an impact on ART. However, the implementation of minority NNRTI-resistant HIV-1 variant analysis in addition to genotypic resistance testing (GRT) cannot be recommended in routine clinical settings. Additional associated risk factors need to be discovered.

Testing Spatial Autocorrelation in Weighted Networks : the Modes Permutation Test

In a weighted spatial network, as specified by an exchange matrix, the variances of the spatial values are inversely proportional to the size of the regions. Spatial values are no more exchangeable under independence, thus weakening the rationale for ordinary permutation and bootstrap tests of spatial autocorrelation. We propose an alternative permutation test for spatial autocorrelation, based upon exchangeable spatial modes, constructed as linear orthogonal combinations of spatial values. The coefficients obtain as eigenvectors of the standardised exchange matrix appearing in spectral clustering, and generalise to the weighted case the concept of spatial filtering for connectivity matrices. Also, two proposals aimed at transforming an acessibility matrix into a exchange matrix with with a priori fixed margins are presented. Two examples (inter-regional migratory flows and binary adjacency networks) illustrate the formalism, rooted in the theory of spectral decomposition for reversible Markov chains.

Replicative phenotyping adds value to genotypic resistance testing in heavily pre-treated HIV-infected individuals--the Swiss HIV Cohort Study.

BACKGROUND: Replicative phenotypic HIV resistance testing (rPRT) uses recombinant infectious virus to measure viral replication in the presence of antiretroviral drugs. Due to its high sensitivity of detection of viral minorities and its dissecting power for complex viral resistance patterns and mixed virus populations rPRT might help to improve HIV resistance diagnostics, particularly for patients with multiple drug failures. The aim was to investigate whether the addition of rPRT to genotypic resistance testing (GRT) compared to GRT alone is beneficial for obtaining a virological response in heavily pre-treated HIV-infected patients. METHODS: Patients with resistance tests between 2002 and 2006 were followed within the Swiss HIV Cohort Study (SHCS). We assessed patients' virological success after their antiretroviral therapy was switched following resistance testing. Multilevel logistic regression models with SHCS centre as a random effect were used to investigate the association between the type of resistance test and virological response (HIV-1 RNA <50 copies/mL or ≥1.5 log reduction). RESULTS: Of 1158 individuals with resistance tests 221 with GRT+rPRT and 937 with GRT were eligible for analysis. Overall virological response rates were 85.1% for GRT+rPRT and 81.4% for GRT. In the subgroup of patients with >2 previous failures, the odds ratio (OR) for virological response of GRT+rPRT compared to GRT was 1.45 (95% CI 1.00-2.09). Multivariate analyses indicate a significant improvement with GRT+rPRT compared to GRT alone (OR 1.68, 95% CI 1.31-2.15). CONCLUSIONS: In heavily pre-treated patients rPRT-based resistance information adds benefit, contributing to a higher rate of treatment success.

Testing demographic models of effective population size.

Due to practical difficulties in obtaining direct genetic estimates of effective sizes, conservation biologists have to rely on so-called 'demographic models' which combine life-history and mating-system parameters with F-statistics in order to produce indirect estimates of effective sizes. However, for the same practical reasons that prevent direct genetic estimates, the accuracy of demographic models is difficult to evaluate. Here we use individual-based, genetically explicit computer simulations in order to investigate the accuracy of two such demographic models aimed at investigating the hierarchical structure of populations. We show that, by and large, these models provide good estimates under a wide range of mating systems and dispersal patterns. However, one of the models should be avoided whenever the focal species' breeding system approaches monogamy with no sex bias in dispersal or when a substructure within social groups is suspected because effective sizes may then be strongly overestimated. The timing during the life cycle at which F-statistics are evaluated is also of crucial importance and attention should be paid to it when designing field sampling since different demographic models assume different timings. Our study shows that individual-based, genetically explicit models provide a promising way of evaluating the accuracy of demographic models of effective size and delineate their field of applicability.

A new alternative method for testing skin irritation using a human skin model: a pilot study.

Studies assessing skin irritation to chemicals have traditionally used laboratory animals; however, such methods are questionable regarding their relevance for humans. New in vitro methods have been validated, such as the reconstructed human epidermis (RHE) model (Episkin®, Epiderm®). The comparison (accuracy) with in vivo results such as the 4-h human patch test (HPT) is 76% at best (Epiderm®). There is a need to develop an in vitro method that better simulates the anatomo-pathological changes encountered in vivo. To develop an in vitro method to determine skin irritation using human viable skin through histopathology, and compare the results of 4 tested substances to the main in vitro methods and in vivo animal method (Draize test). Human skin removed during surgery was dermatomed and mounted on an in vitro flow-through diffusion cell system. Ten chemicals with known non-irritant (heptylbutyrate, hexylsalicylate, butylmethacrylate, isoproturon, bentazon, DEHP and methylisothiazolinone (MI)) and irritant properties (folpet, 1-bromohexane and methylchloroisothiazolinone (MCI/MI)), a negative control (sodiumchloride) and a positive control (sodiumlaurylsulphate) were applied. The skin was exposed at least for 4h. Histopathology was performed to investigate irritation signs (spongiosis, necrosis, vacuolization). We obtained 100% accuracy with the HPT model; 75% with the RHE models and 50% with the Draize test for 4 tested substances. The coefficients of variation (CV) between our three test batches were <0.1, showing good reproducibility. Furthermore, we reported objectively histopathological irritation signs (irritation scale): strong (folpet), significant (1-bromohexane), slight (MCI/MI at 750/250ppm) and none (isoproturon, bentazon, DEHP and MI). This new in vitro test method presented effective results for the tested chemicals. It should be further validated using a greater number of substances; and tested in different laboratories in order to suitably evaluate reproducibility.

Tests pharmacogénétiques: bientôt avant chaque prescription [Pharmacogenetic testing: soon before every prescription?]

Genetic polymorphisms have currently been described in more than 200 systems affecting pharmacological responses (cytochromes P450, conjugation enzymes, transporters, receptors, effectors of response, protection mechanisms, determinants of immunity). Pharmacogenetic testing, i.e. the profiling of individual patients for such variations, is about to become largely available. Recent progress in the pharmacogenetics of tamoxifen, oral anticoagulants and anti-HIV agents is reviewed to discuss critically their potential impact on prescription and contribution/limits for improving rational and safe use of pharmaceuticals. Prospective controlled trials are required to evaluate large-scale pharmacogenetic testing in therapeutics. Ethical, social and psychological issues deserve particular attention.

Investigating barriers in HIV-testing oncology patients. The IBITOP study: phase I.

BACKGROUND: Since the advent of combined antiretroviral therapy (ART), the incidence of non-AIDS-defining cancers (non-ADCs) among HIV-positive patients is rising. We previously described HIV testing rates of <5% in our oncology centre, against a local HIV prevalence of 0.4% (1). We have since worked with the Service of Oncology to identify, how HIV testing can be optimized, we have conducted a study on investigating barriers in HIV-testing oncology patients (IBITOP) among treating oncologists and their patients. METHODS: After an initial two-month pilot study to examine feasibility (2), we conducted the first phase of the IBITOP study between 1st July and 31st October 2013. Patients of unknown HIV status, newly diagnosed with solid-organ non-AIDS-defining cancer, and treated at Lausanne University Hospital were invited to participate. Patients were offered HIV testing as a part of their initial oncology work-up. Oncologist testing proposals and patient acceptance were the primary endpoints. RESULTS: Of 235 patients with a new oncology diagnosis, 10 were excluded (7 with ADCs and 3 of known HIV-positive status). Mean age was 62 years; 48% were men and 71% were Swiss. Of 225 patients, 75 (33%) were offered HIV testing. Of these, 56 (75%) accepted, of whom 52 (93%) were tested. A further ten patients were tested (without documentation of being offered a test), which gave a total testing rate of 28% (62/225). Among the 19 patients who declined testing, reasons cited included self-perceived absence of HIV risk, previous testing and palliative care. Of the 140 patients not offered HIV testing and not tested, reasons were documented for 35 (25%), the most common being previous testing and follow-up elsewhere. None of the 62 patients HIV tested had a reactive test. CONCLUSIONS: In this study, one third of patients seen were offered testing and the HIV testing rate was fivefold higher than that of previously observed in this service. Most patients accepted testing when offered. As HIV-positive status impacts on the medical management of cancer patients, we recommend that HIV screening should be performed in settings, where HIV prevalence is >0.1%. Phase II of the IBITOP study is now underway to explore barriers to HIV screening among oncologists and patients following the updated national HIV testing guidelines which recommend testing in non-ADC patients undergoing chemotherapy.

In-vitro testing of biofilm formation on infected bone grafts and bone substitutes

Background: Bacteria form biofilms on the surface of orthopaedic devices, causing persistent infections. Monitoring biofilm formation on bone grafts and bone substitutes is challenging due to heterogeneous surface characteristics. We analyzed various bone grafts and bone substitutes regarding their propensity for in-vitro biofilm formation caused by S. aureus and S. epidermidis. Methods: Beta-tricalciumphosphate (b-TCP, ChronOsTM), processed human spongiosa (TutoplastTM) and PMMA (PalacosTM) were investigated. PE was added as a growth control. As test strains S. aureus (ATCC 29213) and S. epidermidis RP62A (ATCC 35984) were used. Test materials were incubated with 105 cfu/ml. After 24 h, test materials were removed and washed, followed by a standardised sonication protocol. The resulting sonication fluid was plated and bacterial counts were enumerated and expressed as cfu/sample. Sonicated samples were transferred to a microcalorimeter (TA Instrument) and heat flow monitored over a 24 h period with a precision of 0.0001°C and a sensitiviy of 200 μW. Experiments were performed in triplicates to calculate the mean ± SD. One-way ANOVA analysis was used for statistical analysis. Results: Bacterial counts (log10 cfu/sample) were highest on b-TCP (S. aureus 7.67 ± 0.17; S. epidermidis 8.14 ± 0.05) while bacterial density (log10 cfu/surface) was highest on PMMA (S. aureus 6.12 ± 0.2, S. epidermidis 7.65 ± 0.13). Detection time for S. aureus biofilms was shorter for the porous materials (b-TCP and Tutoplast, p <0.001) compared to the smooth materials (PMMA and PE) with no differences between b-TCP and TutoplastTM (p >0.05) or PMMA and PE (p >0.05). In contrast, for S. epidermidis biofilms the detection time was different (p <0.001) between all materials except between Tutoplast and PE (p >0.05). Conclusion: Our results demonstrate biofilm formation with both strains on all tested materials. Microcalorimetry was able to detect quantitatively the amount of biofilm. Further studies are needed to see whether calorimetry is a suitable tool also to monitor approaches to prevent and treat infections associated with bone grafts and bone substitutes.