Optimal culture incubation time in orthopedic device-associated infections: a retrospective analysis of prolonged 14-day incubation.

Accurate diagnosis of orthopedic device-associated infections can be challenging. Culture of tissue biopsy specimens is often considered the gold standard; however, there is currently no consensus on the ideal incubation time for specimens. The aim of our study was to assess the yield of a 14-day incubation protocol for tissue biopsy specimens from revision surgery (joint replacements and internal fixation devices) in a general orthopedic and trauma surgery setting. Medical records were reviewed retrospectively in order to identify cases of infection according to predefined diagnostic criteria. From August 2009 to March 2012, 499 tissue biopsy specimens were sampled from 117 cases. In 70 cases (59.8%), at least one sample showed microbiological growth. Among them, 58 cases (82.9%) were considered infections and 12 cases (17.1%) were classified as contaminations. The median time to positivity in the cases of infection was 1 day (range, 1 to 10 days), compared to 6 days (range, 1 to 11 days) in the cases of contamination (P < 0.001). Fifty-six (96.6%) of the infection cases were diagnosed within 7 days of incubation. In conclusion, the results of our study show that the incubation of tissue biopsy specimens beyond 7 days is not productive in a general orthopedic and trauma surgery setting. Prolonged 14-day incubation might be of interest in particular situations, however, in which the prevalence of slow-growing microorganisms and anaerobes is higher.

Early intensification and autologous stem cell transplantation in patients with systemic AL amyloidosis: a single-centre experience.

Primary systemic amyloidosis (AL amyloidosis) continues to have a very poor prognosis. Most therapeutic strategies remain unsatisfactory. Conventional chemotherapy is known to offer at best only moderate efficacy. Several studies have yielded higher complete response rates after high-dose chemotherapy and autologous stem cell transplantation (ASCT) in addition to improving outcomes in a subgroup of patients. However, the superiority of an intensive approach in AL amyloidosis has not been confirmed in a randomised trial. The precise role of ASCT remains unclear. We report our experience in 16 patients diagnosed with AL amyloidosis and treated in a multidisciplinary approach with high-dose melphalan and ASCT. Median age was 59 (39-71) years. The kidneys were predominantly affected in 75% of cases; two or more organs were affected in 38%. Median time from diagnosis to transplantation was 2 (1-4) months. Three patients (19%) developed acute renal failure and required transient dialysis. Transplant-related mortality was 6% after 100 days. Haematological complete response (CR) was obtained in nine (56%) and organ response in six (38%) patients. Nine out of 12 patients (75%) with kidney involvement exhibited a sustained clinical benefit at 12 months. Half of all the patients (n = 8) were alive after a median follow-up of 33 months, including two in continuous CR. This suggests that high-dose chemotherapy and ASCT are still valid treatment options in AL amyloidosis and that a significant number of patients with renal involvement might benefit from this approach.

La "bientraitance", exploration du concept et essai d'utilisation en santé publique: une expérience à Fribourg (Suisse). ["Bientraitance": conceptual exploration and an example of its application in public health: an experience from Fribourg, Switzerland]

Since the year 2000, the concept of "bientraitance" (for which no equivalent term has yet emerged in either the English or German language) has gained widespread credence among educators, sociologists and health professionals in France and Belgium. This concept emphasizes a constructive approach to care and education rather than merely one of prevention of disasters. Applied in public health, and in particular to mental health promotion, the use of the concept of "bientraitance" can help promote both effectiveness and meaning in the design and planning of community interventions. The article presents an example of an intervention for children and adolescents in Fribourg, Switzerland. The underpinning hypothesis is that the children and youth groups (such as sports clubs, artistic and cultural associations, scouts and guides) represent largely untapped, or under-tapped, informal health resources with a favourable cost-effectiveness profile. "Bientraitance" criteria are used in selecting certain associations offering structured extracurricular group educational activities and collective out-of-school (or after school) programmes. Support is provided to the organisations selected for recruiting new members, in particular those with potentially lower levels of access, for example disabled children or new migrants. The results will be evaluated for the impact of participation in various out-of-school activities on health and health determinants from a prospective and comparative perspective. This paper shows how the concept of "bientraitance" can be useful in the development of a public health intervention.

Optimal CD8 T cell responsiveness is controlled within a defined TCR affinity window

Protective immune responses relyon TCR-mediated recognition of antigenspresented by MHC molecules. Tcells directed against tumor antigensare thought to express TCRs of loweraffinity/avidity than pathogen-specificT lymphocytes. An attractivestrategy to improve anti-tumor T cellresponses is to adoptively transferCD8+ T cells engineered with TCRsof optimized affinity. However, themechanisms that control optimal Tcell activation and responsiveness remainpoorly defined. We aim at characterizingTCR-pMHC binding parametersand downstream signalingevents that regulate T cell functionalityby using an in silico designedpanel of tumor antigen-specific TCRsof incremental affinity for pMHC(Kd100 M- 15 nM).We found that optimalT cell responses (cytokine secretionand target cell killing) occurredwithin a well-defined window ofTCR-pMHC binding affinity (5 M-1 M), while drastic functional declinewas detected in T cells expressingvery low and very high TCRaffinities,which was not caused by any increasein apoptosis. Whole-genomemicroarray analysis revealed that Tcells with optimal TCR affinitieshighly up-regulated transcription ofgenes typical of T cell activation (i.e.IFN-, NF-B and TNFR), while reducedexpression was detected in Tcells of very low or very high TCR affinity.Strikingly, hierarchical clusteringshowed that the latter two variantsclustered together with the un-stimulatedcontrol Tcells.Yet, despite commonclustering, several genes seemedto be differentially expressed, suggestingthat the mechanisms involvedin this "unresponsiveness state" maydiffer between those two variants. Finally,calcium influx assays also demonstratedattenuated responses in Tcells of very high TCR affinity. Ourresults indicate that optimal T cellfunction is tightly controlled within adefinedTCRaffinity window throughvery proximal TCR-mediated mechanisms,possibly at the TCR-pMHCbinding interface. Uncovering themechanisms regulating optimal/maximalT cell function is essential to understandand promote therapeutic designlike adoptive T cell therapy.

Genetic abnormalities and survival in multiple myeloma: the experience of the Intergroupe Francophone du Myélome.

Acquired genomic aberrations have been shown to significantly impact survival in several hematologic malignancies. We analyzed the prognostic value of the most frequent chromosomal changes in a large series of patients with newly diagnosed symptomatic myeloma prospectively enrolled in homogeneous therapeutic trials. All the 1064 patients enrolled in the IFM99 trials conducted by the Intergroupe Francophone du Myélome benefited from an interphase fluorescence in situ hybridization analysis performed on purified bone marrow plasma cells. They were systematically screened for the following genomic aberrations: del(13), t(11;14), t(4;14), hyperdiploidy, MYC translocations, and del(17p). Chromosomal changes were observed in 90% of the patients. The del(13), t(11;14), t(4;14), hyperdiploidy, MYC translocations, and del(17p) were present in 48%, 21%, 14%, 39%, 13%, and 11% of the patients, respectively. After a median follow-up of 41 months, univariate statistical analyses revealed that del(13), t(4;14), nonhyperdiploidy, and del(17p) negatively impacted both the event-free survival and the overall survival, whereas t(11;14) and MYC translocations did not influence the prognosis. Multivariate analyses on 513 patients annotated for all the parameters showed that only t(4;14) and del(17p) retained prognostic value for both the event-free and overall survivals. When compared with the currently used International Staging System, this prognostic model compares favorably. In myeloma, the genomic aberrations t(4;14) and del(17p), together with beta2-microglobulin level, are important independent predictors of survival. These findings have implications for the design of risk-adapted treatment strategies.

Vulnerability to schizophrenia: relevance of patients' subjective experience for empirical and clinical work.

Efforts are being made by clinicians and researchers to accurately delineate phenotypic traits of individuals at enhanced risk of schizophrenia. This issue is important for a better understanding of the etiopathogenic mechanisms of the disease and for the building up of programs of primary prevention. We suggest that disturbances of subjective experience, although difficult to operationalize, are an important-but until now neglected-core component of schizophrenia spectrum disorders. We advocate the development of valid and reliable instruments in order to allow the assessment of basic symptoms and disturbances of Self-experience. Delineation of vulnerability to schizophrenia cannot rely solely on neuropsychological and neurophysiological data, as prevention programs will be performed mainly by clinicians.

Leverage and beliefs: Personal experience and risk taking in margin lending

What determines risk-bearing capacity and the amount of leverage in financial markets? Thispaper uses unique micro-data on collateralized lending contracts during a period of financialdistress to address this question. An investor syndicate speculating in English stocks wentbankrupt in 1772. Using hand-collected information from Dutch notarial archives, we examinechanges in lenders' behavior following exposure to potential (but not actual) losses. Before thedistress episode, financiers that lent to the ill-fated syndicate were indistinguishable from therest. Afterwards, they behaved differently: they lent with much higher haircuts. Only lendersexposed to the failed syndicate altered their behavior. The differential change is remarkable sincethe distress was public knowledge, and because none of the lenders suffered actual losses ? allfinanciers were repaid in full. Interest rates were also unaffected; the market balanced solelythrough changes in collateral requirements. Our findings are consistent with a heterogeneousbeliefs-interpretation of leverage. They also suggest that individual experience can modify thelevel of leverage in a market quickly.

Experience and endocrine stress responses in neonatal and pediatric critical care nurses and physicians.

OBJECTIVE: Critical care is a working environment with frequent exposure to stressful events. High levels of psychological stress have been associated with increased prevalence of burnout. Psychological distress acts as a potent trigger of cortisol secretions. We attempted to objectify endocrine stress reactivity. DESIGN: Observational cohort study during two 12-day periods in successive years. SETTING: A tertiary multidisciplinary neonatal and pediatric intensive care unit (33 beds). SUBJECTS: One hundred and twelve nurses and 27 physicians (94% accrual rate). INTERVENTIONS AND MEASUREMENTS: Cortisol determined from salivary samples collected every 2 hrs and after stressful events. Participants recorded the subjective perception of stress with every sample. Endocrine reactions were defined as transient surges in cortisol of &gt;50% and 2.5 nmol/L over the baseline. MAIN RESULTS: During 7,145 working hours, we observed 474 (12.5%) endocrine reactions from 3,781 samples. The mean cortisol increase amounted to 10.6 nmol/L (219%). The mean occurrence rate of endocrine reactions per subject and sample was 0.159 (range, 0-0.43). Although the mean raw cortisol levels were lower in experienced team members (&gt;3 yrs of intensive care vs. &lt;3 yrs, 4.1 vs. 4.95 nmol/L, p &lt; .001), professional experience failed to attenuate the frequency and magnitude of endocrine reactions, except for the subgroup of nurses and physicians with &gt;8 yrs of intensive care experience. A high proportion (71.3%) of endocrine reactions occurred without conscious perception of stress. Unawareness of stress was higher in intensive care nurses (75.1%) than in intermediate care nurses (51.8%, p &lt; .01). CONCLUSIONS: Stress-related cortisol surges occur frequently in neonatal and pediatric critical care staff. Cortisol increases are independent of subjective stress perception. Professional experience does not abate the endocrine stress reactivity.

Implementation Manual — 3D Engineered Models for Highway Construction: The Iowa Experience; RB33-014, 2015

3D engineered modeling is a relatively new and developing technology that can provide numerous benefits to owners, engineers, contractors, and the general public. This manual is for highway agencies that are considering or are in the process of switching from 2D plan sets to 3D engineered models in their highway construction projects. It will discuss some of the benefits, applications, limitations, and implementation considerations for 3D engineered models used for survey, design, and construction. Note that is not intended to cover all eventualities in all states regarding the deployment of 3D engineered models for highway construction. Rather, it describes how one state—Iowa—uses 3D engineered models for construction of highway projects, from planning and surveying through design and construction.

Telemedicine Experience for Chronic Care in COPD

Information and telecommunication technologies are called to play a major role in the changes that healthcare systems have to face to cope with chronic disease. This paper reports a telemedicine experience for the home care of chronic patients suffering from chronic obstructive pulmonary disease (COPD) and an integrated system designed to carry out this experience. To determine the impact on health, the chronic care telemedicine system was used during one year (2002) with 157 COPD patients in a clinical experiment; endpoints were readmissions and mortality. Patients in the intervention group were followed up at their homes and could contact the care team at any time through the call center. The care team shared a unique electronic chronic patient record (ECPR) accessible through the web-based patient management module or the home visit units. Results suggest that integrated home telemedicine services can support health professionals caring for patients with chronic disease, and improve their health.We have found that simple telemedicine services (ubiquitous access to ECPR, ECPR shared by care team, accessibility to case manager, problem reporting integrated in ECPR) can increase the number of patients that were not readmitted (51% intervention, 33% control), are acceptable to professionals, and involve low installation and exploitation costs. Further research is needed to determine the role of telemonitoring and televisit services for this kind of patients.

Maximising the duration of disease control in metastatic renal cell carcinoma with targeted agents: an expert agreement.

With six targeted agents approved (sorafenib, sunitinib, temsirolimus, bevacizumab [+interferon], everolimus and pazopanib), many patients with metastatic renal cell carcinoma (mRCC) will receive multiple therapies. However, the optimum sequencing approach has not been defined. A group of European experts reviewed available data and shared their clinical experience to compile an expert agreement on the sequential use of targeted agents in mRCC. To date, there are few prospective studies of sequential therapy. The mammalian target of rapamycin (mTOR) inhibitor everolimus was approved for use in patients who failed treatment with inhibitors of vascular endothelial growth factor (VEGF) and VEGF receptors (VEGFR) based on the results from a Phase III placebo-controlled study; however, until then, the only licensed agents across the spectrum of mRCC were VEGF(R) inhibitors (sorafenib, sunitinib and bevacizumab + interferon), and as such, a large body of evidence has accumulated regarding their use in sequence. Data show that sequential use of VEGF(R) inhibitors may be an effective treatment strategy to achieve prolonged clinical benefit. The optimal place of each targeted agent in the treatment sequence is still unclear, and data from large prospective studies are needed. The Phase III AXIS study of second-line sorafenib vs. axitinib (including post-VEGF(R) inhibitors) has completed, but the data are not yet published; other ongoing studies include the Phase III SWITCH study of sorafenib-sunitinib vs. sunitinib-sorafenib (NCT00732914); the Phase III 404 study of temsirolimus vs. sorafenib post-sunitinib (NCT00474786) and the Phase II RECORD 3 study of sunitinib-everolimus vs. everolimus-sunitinib (NCT00903175). Until additional data are available, consideration of patient response and tolerability to treatment may facilitate current decision-making regarding when to switch and which treatment to switch to in real-life clinical practice.