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.

Comparison of the diagnostic performance of the original and modified Wells score in inpatients and outpatients with suspected deep vein thrombosis.

Introduction: The original and modified Wells score are widely used prediction rules for pre-test probability assessment of deep vein thrombosis (DVT). The objective of this study was to compare the predictive performance of both Wells scores in unselected patients with clinical suspicion of DVT.Methods: Consecutive inpatients and outpatients with a clinical suspicion of DVT were prospectively enrolled. Pre-test DVT probability (low/intermediate/high) was determined using both scores. Patients with a non-high probability based on the original Wells score underwent D-dimers measurement. Patients with D-dimers <500 mu g/L did not undergo further testing, and treatment was withheld. All others underwent complete lower limb compression ultrasound, and those diagnosed with DVT were anticoagulated. The primary study outcome was objectively confirmed symptomatic venous thromboembolism within 3 months of enrollment.Results: 298 patients with suspected DVT were included. Of these, 82 (27.5%) had DVT, and 46 of them were proximal. Compared to the modified score, the original Wells score classified a higher proportion of patients as low-risk (53 vs 48%; p<0.01) and a lower proportion as high-risk (17 vs 15%; p=0.02); the prevalence of proximal DVT in each category was similar with both scores (7-8% low, 16-19% intermediate, 36-37% high). The area under the receiver operating characteristic curve regarding proximal DVT detection was similar for both scores, but they both performed poorly in predicting isolated distal DVT and DVT in inpatients.Conclusion: The study demonstrates that both Wells scores perform equally well in proximal DVT pre-test probability prediction. Neither score appears to be particularly useful in hospitalized patients and those with isolated distal DVT. (C) 2011 Elsevier Ltd. All rights reserved.

Development and validation of a clinical decision rule for the diagnosis of influenza.

INTRODUCTION: A clinical decision rule to improve the accuracy of a diagnosis of influenza could help clinicians avoid unnecessary use of diagnostic tests and treatments. Our objective was to develop and validate a simple clinical decision rule for diagnosis of influenza. METHODS: We combined data from 2 studies of influenza diagnosis in adult outpatients with suspected influenza: one set in California and one in Switzerland. Patients in both studies underwent a structured history and physical examination and had a reference standard test for influenza (polymerase chain reaction or culture). We randomly divided the dataset into derivation and validation groups and then evaluated simple heuristics and decision rules from previous studies and 3 rules based on our own multivariate analysis. Cutpoints for stratification of risk groups in each model were determined using the derivation group before evaluating them in the validation group. For each decision rule, the positive predictive value and likelihood ratio for influenza in low-, moderate-, and high-risk groups, and the percentage of patients allocated to each risk group, were reported. RESULTS: The simple heuristics (fever and cough; fever, cough, and acute onset) were helpful when positive but not when negative. The most useful and accurate clinical rule assigned 2 points for fever plus cough, 2 points for myalgias, and 1 point each for duration <48 hours and chills or sweats. The risk of influenza was 8% for 0 to 2 points, 30% for 3 points, and 59% for 4 to 6 points; the rule performed similarly in derivation and validation groups. Approximately two-thirds of patients fell into the low- or high-risk group and would not require further diagnostic testing. CONCLUSION: A simple, valid clinical rule can be used to guide point-of-care testing and empiric therapy for patients with suspected influenza.

ESCMID* guideline for the diagnosis and management of Candida diseases 2012: diagnostic procedures.

As the mortality associated with invasive Candida infections remains high, it is important to make optimal use of available diagnostic tools to initiate antifungal therapy as early as possible and to select the most appropriate antifungal drug. A panel of experts of the European Fungal Infection Study Group (EFISG) of the European Society of Clinical Microbiology and Infectious Diseases (ESCMID) undertook a data review and compiled guidelines for the clinical utility and accuracy of different diagnostic tests and procedures for detection of Candida infections. Recommendations about the microbiological investigation and detection of candidaemia, invasive candidiasis, chronic disseminated candidiasis, and oropharyngeal, oesophageal, and vaginal candidiasis were included. In addition, remarks about antifungal susceptibility testing and therapeutic drug monitoring were made.

Investigations on hydrogen isotope ratios of endogenous urinary steroids: reference-population-based thresholds and proof-of-concept.

Carbon isotope ratio (CIR) analysis has been routinely and successfully used in sports drug testing for many years to uncover the misuse of endogenous steroids. One limitation of the method is the availability of steroid preparations exhibiting CIRs equal to endogenous steroids. To overcome this problem, hydrogen isotope ratios (HIR) of endogenous urinary steroids were investigated as a potential complement; results obtained from a reference population of 67 individuals are presented herein. An established sample preparation method was modified and improved to enable separate measurements of each analyte of interest where possible. From the fraction of glucuronidated steroids; pregnanediol, 16-androstenol, 11-ketoetiocholanolone, androsterone (A), etiocholanolone (E), dehydroepiandrosterone (D), 5α- and 5β-androstanediol, testosterone and epitestosterone were included. In addition, sulfate conjugates of A, E, D, epiandrosterone and 17α- and 17β-androstenediol were considered and analyzed after acidic solvolysis. The obtained results enabled the calculation of the first reference-population-based thresholds for HIR of urinary steroids that can readily be applied to routine doping control samples. Proof-of-concept was accomplished by investigating urine specimens collected after a single oral application of testosterone-undecanoate. The HIR of most testosterone metabolites were found to be significantly influenced by the exogenous steroid beyond the established threshold values. Additionally, one regular doping control sample with an extraordinary testosterone/epitestosterone ratio of 100 without suspicious CIR was subjected to the complementary methodology of HIR analysis. The HIR data eventually provided evidence for the exogenous origin of urinary testosterone metabolites. Despite further investigations on HIR being advisable to corroborate the presented reference-population-based thresholds, the developed method proved to be a new tool supporting modern sports drug testing procedures.

Gastric banding interferes with esophageal motility and gastroesophageal reflux.

BACKGROUND: Gastroesophageal reflux and progressive esophageal dilatation can develop after gastric banding (GB). HYPOTHESIS: Gastric banding may interfere with esophageal motility, enhance reflux, or promote esophageal dilatation. DESIGN: Before-after trial in patients undergoing GB. SETTING: University teaching hospital. PATIENTS AND METHODS: Between January 1999 and August 2002, 43 patients undergoing laparoscopic GB for morbid obesity underwent upper gastrointestinal endoscopy, 24-hour pH monitoring, and stationary esophageal manometry before GB and between 6 and 18 months postoperatively. MAIN OUTCOME MEASURES: Reflux symptoms, endoscopic esophagitis, pressures measured at manometry, esophageal acid exposure. RESULTS: There was no difference in the prevalence of reflux symptoms or esophagitis before and after GB. The lower esophageal sphincter was unaffected by surgery, but contractions in the lower esophagus weakened after GB, in correlation with preoperative values. There was a trend toward more postoperative nonspecific motility disorders. Esophageal acid exposure tended to decrease after GB, with fewer reflux episodes. A few patients developed massive postoperative reflux. There was no clear correlation between preoperative testing and postoperative esophageal acid exposure, although patients with abnormal preoperative acid exposure tended to maintain high values after GB. CONCLUSIONS: Postoperative esophageal dysmotility and gastroesophageal reflux are not uncommon after GB. Preoperative testing should be done routinely. Low amplitude of contraction in the lower esophagus and increased esophageal acid exposure should be regarded as contraindications to GB. Patients with such findings should be offered an alternative procedure, such as Roux-en-Y gastric bypass.

Design and Evaluation of a Single-Span Bridge Using Ultra- High Performance Concrete, September 2009

Research presented herein describes an application of a newly developed material called Ultra-High Performance Concrete (UHPC) to a single-span bridge. The two primary objectives of this research were to develop a shear design procedure for possible code adoption and to provide a performance evaluation to ensure the viability of the first UHPC bridge in the United States. Two other secondary objectives included defining of material properties and understanding of flexural behavior of a UHPC bridge girder. In order to obtain information in these areas, several tests were carried out including material testing, large-scale laboratory flexure testing, large-scale laboratory shear testing, large-scale laboratory flexure-shear testing, small-scale laboratory shear testing, and field testing of a UHPC bridge. Experimental and analytical results of the described tests are presented. Analytical models to understand the flexure and shear behavior of UHPC members were developed using iterative computer based procedures. Previous research is referenced explaining a simplified flexural design procedure and a simplified pure shear design procedure. This work describes a shear design procedure based on the Modified Compression Field Theory (MCFT) which can be used in the design of UHPC members. Conclusions are provided regarding the viability of the UHPC bridge and recommendations are made for future research.

The immune space: a concept and template for rationalizing vaccine development.

Abstract Empirical testing of candidate vaccines has led to the successful development of a number of lifesaving vaccines. The advent of new tools to manipulate antigens and new methods and vectors for vaccine delivery has led to a veritable explosion of potential vaccine designs. As a result, selection of candidate vaccines suitable for large-scale efficacy testing has become more challenging. This is especially true for diseases such as dengue, HIV, and tuberculosis where there is no validated animal model or correlate of immune protection. Establishing guidelines for the selection of vaccine candidates for advanced testing has become a necessity. A number of factors could be considered in making these decisions, including, for example, safety in animal and human studies, immune profile, protection in animal studies, production processes with product quality and stability, availability of resources, and estimated cost of goods. The "immune space template" proposed here provides a standardized approach by which the quality, level, and durability of immune responses elicited in early human trials by a candidate vaccine can be described. The immune response profile will demonstrate if and how the candidate is unique relative to other candidates, especially those that have preceded it into efficacy testing and, thus, what new information concerning potential immune correlates could be learned from an efficacy trial. A thorough characterization of immune responses should also provide insight into a developer's rationale for the vaccine's proposed mechanism of action. HIV vaccine researchers plan to include this general approach in up-selecting candidates for the next large efficacy trial. This "immune space" approach may also be applicable to other vaccine development endeavors where correlates of vaccine-induced immune protection remain unknown.

The characteristics of gait in Charcot-Marie-Tooth disease types I and II.

Certain typical gait characteristics such as foot-drop and foot supination are well described in Charcot-Marie-Tooth disease. These are directly related to the primary disease and due to the weakness of ankle dorsiflexors and everters characteristic of this hereditary neuropathy. We analysed 16 subjects aged 8-52 years old (11 with type I, 5 with type II Charcot-Marie-Tooth disease) using three-dimensional gait analysis and identified kinematic features previously unreported. These patients showed a combination of tight tendo achillei, foot-drop, failure of plantar flexion and increased foot supination, but also presented with excessive internal rotation of the knee and/or tibia, knee hyperextension in stance, excessive external rotation at the hips and decreased hip adduction in stance (typical of a broad based gait). These proximal features could have been an adaptation to or consequence of the disrupted ankle and foot biomechanics, however a direct relation to the neuropathy is also possible since sub-normal muscle power was observed at the proximal levels in most subjects on both manual testing and kinetic analysis. Gait analysis is a useful tool in defining the characteristic gait of patients with Charcot-Marie-Tooth disease.

Nanotechnology: balancing benefits and risks to public health and the environment : expert paper

Nanotechnology has been heralded as a "revolution" in science, for two reasons: first, because of its revolutionary view of the way in which chemicals and elements, such as gold and silver, behave, compared to traditional scientific understanding of their properties. Second, the impact of these new discoveries, as applied to commerce, can transform the daily life of consumer products ranging from sun tan lotions and cosmetics, food packaging and paints and coatings for cars, housing and fabrics, medicine and thousands of industrial processes.9 Beneficial consumer use of nanotechnologies, already in the stream of commerce, improves coatings on inks and paints in everything from food packaging to cars. Additionally, "Nanomedicine" offers the promise of diagnosis and treatment at the molecular level in order to detect and treat presymptomatic disease,10 or to rebuild neurons in Alzheimer's and Parkinson's disease. There is a possibility that severe complications such as stroke or heart attack may be avoided by means of prophylactic treatment of people at risk, and bone regeneration may keep many people active who never expected rehabilitation. Miniaturisation of diagnostic equipment can also reduce the amount of sampling materials required for testing and medical surveillance. Miraculous developments, that sound like science fiction to those people who eagerly anticipate these medical products, combined with the emerging commercial impact of nanotechnology applications to consumer products will reshape civil society - permanently. Thus, everyone within the jurisdiction of the Council of Europe is an end-user of nanotechnology, even without realising that nanotechnology has touched daily life.

Precast Concrete Elements for Accelerated Bridge Construction Final Report, Volume 1-1. Laboratory Testing of Precast Substructure Components: Boone County Bridge, January 2009

In July 2006, construction began on an accelerated bridge project in Boone County, Iowa that was composed of precast substructure elements and an innovative, precast deck panel system. The superstructure system consisted of full-depth deck panels that were prestressed in the transverse direction, and after installation on the prestressed concrete girders, post-tensioned in the longitudinal direction. Prior to construction, laboratory tests were completed on the precast abutment and pier cap elements. The substructure testing was to determine the punching shear strength of the elements. Post-tensioning testing and verification of the precast deck system was performed in the field. The forces in the tendons provided by the contractor were verified and losses due to the post-tensioning operation were measured. The stress (strain) distribution in the deck panels due to the post-tensioning was also measured and analyzed. The entire construction process for this bridge system was documented. Representatives from the Boone County Engineers Office, the prime contractor, precast fabricator, and researchers from Iowa State University provided feedback and suggestions for improving the constructability of this design.

Demonstration of Load Rating Capabilities through Physical Load Testing: Sioux County Bridge Case Study, RB32-013, 2013

The objective of this work, Pilot Project - Demonstration of Capabilities and Benefits of Bridge Load Rating through Physical Testing, was to demonstrate the capabilities for load testing and rating bridges in Iowa, study the economic benefit of performing such testing, and perform outreach to local, state, and national engineers on the topic of bridge load testing and rating. This report documents one of three bridges inspected, load tested, and load rated as part of the project, the Sioux County Bridge (FHWA #308730), including testing procedures and performance of the bridge under static loading along with the calculated load rating from the field-calibrated analytical model. Two parallel reports document the testing and load rating of the Ida County Bridge (FHWA #186070) and the Johnson County Bridge (FHWA #205750). A tech brief provides overall information about the project.

Demonstration of Load Rating Capabilities through Physical Load Testing: Ida County Bridge Case Study, RB32-013, 2013

The objective of this work, Pilot Project - Demonstration of Capabilities and Benefits of Bridge Load Rating through Physical Testing, was to demonstrate the capabilities for load testing and rating bridges in Iowa, study the economic benefit of performing such testing, and perform outreach to local, state, and national engineers on the topic of bridge load testing and rating. This report documents one of three bridges inspected, load tested, and load rated as part of the project, the Ida County Bridge (FHWA #186070), including testing procedures and performance of the bridge under static loading along with the calculated load rating from the field-calibrated analytical model. Two parallel reports document the testing and load rating of the Sioux County Bridge (FHWA #308730) and the Johnson County Bridge (FHWA #205750). A tech brief provides overall information about the project.

Demonstration of Load Rating Capabilities through Physical Load Testing: Johnson County Bridge Case Study, RB32-013, 2013

The objective of this work, Pilot Project - Demonstration of Capabilities and Benefits of Bridge Load Rating through Physical Testing, was to demonstrate the capabilities for load testing and rating bridges in Iowa, study the economic benefit of performing such testing, and perform outreach to local, state, and national engineers on the topic of bridge load testing and rating. This report documents one of three bridges inspected, load tested, and load rated as part of the project, the Johnson County Bridge (FHWA #205750), including testing procedures and performance of the bridge under static loading along with the calculated load rating from the field-calibrated analytical model. Two parallel reports document the testing and load rating of the Sioux County Bridge (FHWA #308730) and the Ida County Bridge (FHWA #186070). A tech brief provides overall information about the project.

Demonstration of Load Rating Capabilities through Physical Load Testing (4 vol), RB32-013, 2013

The objective of this work, Pilot Project - Demonstration of Capabilities and Benefits of Bridge Load Rating through Physical Testing, was to demonstrate the capabilities for load testing and rating bridges in Iowa, study the economic benefit of performing such testing, and perform outreach to local, state, and national engineers on the topic of bridge load testing and rating. The three final reports document one each of three bridges inspected, load tested, and load rated as part of the project. The bridges include the Sioux County Bridge (FHWA #308730), the Ida County Bridge (FHWA #186070), and the Johnson County Bridge (FHWA #205750). Actions included testing procedures and performance of the bridge under static loading along with the calculated load rating from the field-calibrated analytical model. A Tech Transfer Summary provides overall information about the project.