Introducing cell-free DNA noninvasive testing in a Down syndrome public health screening program: a budget impact analysis.

BACKGROUND: Non-invasive prenatal testing (NIPT) using cell-free fetal DNA in maternal plasma is a high accurate test for prenatal screening for Down syndrome. Although it has been reported to be cost effective as a contingent test, evidence about its budget impact is lacking. OBJECTIVE: To evaluate, using computer simulations, the budget impact of implementing NIPT as a contingent test in the Quebec Program of screening for Trisomy 21. METHODS: A semi-Markov analytic model built to simulate the budget impact of implementing NIPT into the current Quebec Trisomy 21 public Prenatal Screening, Serum Integrated prenatal screening (SIPS). Comparisons were made for a virtual population similar to that of expected Quebec pregnant women in 2015 in terms of size and age. Data input parameters were retrieved from a thorough literature search and in government databases, especially data from Quebec Program of screening for Trisomy 21. The 2015-2016 fiscal year budget impact was estimated from the Quebec healthcare system perspective and was expressed as the difference in the overall costs between the two alternatives (SIPS minus SPS + NIPT). RESULTS: Our study found that, at a baseline cost for NIPT of CAD$ 795, NIPT as a second-tier test offered to high-risk women identified by current screening program (SIPS + NIPT) may be affordable for Quebec health care system. Compared to the current screening program, it would be implemented at a neutral cost, considering a modest annual savings of $ 80,432 (95% CI $ 79, $ 874-$ 81,462). Results were sensitive to the NIPT costs and the uptake-rate of invasive diagnostic tests. CONCLUSION: Introducing NIPT as a contingent test in the Quebec Trisomy 21 screening program is an affordable strategy compared to the current practice. Further research is needed to confirm if our results can be reproduced in other healthcare jurisdictions.

Voxel-based identification of local recurrence sub-regions from pre-treatment PET/CT for locally advanced head and neck cancers.

BACKGROUND: Overall, 40% of patients with a locally advanced head and neck cancer (LAHNC) treated by chemoradiotherapy (CRT) present local recurrence within 2 years after the treatment. The aims of this study were to characterize voxel-wise the sub-regions where tumor recurrence appear and to predict their location from pre-treatment 18F-fluorodeoxyglucose (FDG) positron emission tomography (PET) images. MATERIALS AND METHODS: Twenty-six patients with local failure after treatment were included in this study. Local recurrence volume was identified by co-registering pre-treatment and recurrent PET/CT images using a customized rigid registration algorithm. A large set of voxel-wise features were extracted from pre-treatment PET to train a random forest model allowing to predict local recurrence at the voxel level. RESULTS: Out of 26 expert-assessed registrations, 15 provided enough accuracy to identify recurrence volumes and were included for further analysis. Recurrence volume represented on average 23% of the initial tumor volume. The MTV with a threshold of 50% of SUVmax plus a 3D margin of 10 mm covered on average 89.8% of the recurrence and 96.9% of the initial tumor. SUV and MTV alone were not sufficient to identify the area of recurrence. Using a random forest model, 15 parameters, combining radiomics and spatial location, were identified, allowing to predict the recurrence sub-regions with a median area under the receiver operating curve of 0.71 (range 0.14-0.91). CONCLUSION: As opposed to regional comparisons which do not bring enough evidence for accurate prediction of recurrence volume, a voxel-wise analysis of FDG-uptake features suggested a potential to predict recurrence with enough accuracy to consider tailoring CRT by dose escalation within likely radioresistant regions.

A new method for investigating the relationship between diet and mortality: hazard analysis using dietary isotopes.

Background: The population of Roman Britain are renowned for having elevated nitrogen (δ15) stable isotope values, which have been interpreted as evidence for the increased consumption of marine products. However, such results are now understood to also reflect episodes of stress and disease, suggesting that new interpretations are warranted.Aim: To test a novel approach which combines hazard mortality analysis and stable isotope data to determine whether there is a relationship between age-at-death, elevated δ15N values and mortality risk.Subjects and methods: This study used published osteological and dietary stable isotope data for nitrogen (δ15N) and carbon (δ13C) of 659 1st-5th century AD individuals aged >12 years old excavated from Roman cemeteries in Britain. The relationship between diet and mortality risk was assessed using the Gompertz hazard model, and differences in median reported isotope values between the sexes was determined using a Mann Whitney test.Results: It was discovered that higher δ15N levels are associated with elevated risks of mortality, whereas the opposite pattern was observed for δ13C, and males had higher median δ13C and δ15N values.Conclusion: This study successfully demonstrated that stable isotope data can be integrated into hazard models, allowing one to connect diet and mortality in past populations. It supports the findings of other isotope studies which have established that individuals with childhood stress/trauma will have different isotope patterns.

Multi T1-weighted contrast MRI with fluid and white matter suppression at 1.5 T.

INTRODUCTION: The fluid and white matter suppression sequence (FLAWS) provides two T1-weighted co-registered datasets: a white matter (WM) suppressed contrast (FLAWS1) and a cerebrospinal fluid (CSF) suppressed contrast (FLAWS2). FLAWS has the potential to improve the contrast of the subcortical brain regions that are important for Deep Brain Stimulation surgery planning. However, to date FLAWS has not been optimized for 1.5 T. In this study, the FLAWS sequence was optimized for use at 1.5 T. In addition, the contrast-enhancement properties of FLAWS image combinations were investigated using two voxel-wise FLAWS combined images: the division (FLAWS-div) and the high contrast (FLAWS-hc) image. METHODS: FLAWS sequence parameters were optimized for 1.5 T imaging using an approach based on the use of a profit function under constraints for brain tissue signal and contrast maximization. MR experiments were performed on eleven healthy volunteers (age 18-30). Contrast (CN) and contrast to noise ratio (CNR) between brain tissues were measured in each volunteer. Furthermore, a qualitative assessment was performed to ensure that the separation between the internal globus pallidus (GPi) and the external globus pallidus (GPe) is identifiable in FLAWS1. RESULTS: The optimized set of sequence parameters for FLAWS at 1.5 T provided contrasts similar to those obtained in a previous study at 3 T. The separation between the GPi and the GPe was clearly identified in FLAWS1. The CN of FLAWS-hc was higher than that of FLAWS1 and FLAWS2, but was not different from the CN of FLAWS-div. The CNR of FLAWS-hc was higher than that of FLAWS-div. CONCLUSION: Both qualitative and quantitative assessments validated the optimization of the FLAWS sequence at 1.5 T. Quantitative assessments also showed that FLAWS-hc provides an enhanced contrast compared to FLAWS1 and FLAWS2, with a higher CNR than FLAWS-div.

Passive, non-intrusive assay of depleted uranium.

The ability to detect neutrons from the spontaneous fission of 238U in samples of depleted uranium with organic liquid scintillation detectors is presented. In this paper we introduce a small modular organic liquid scintillator detector array that can detect changes in mass of 238U between 3.69 g and 14.46 g. To do this, 18-h assays of various masses of 0.3% wt. of depleted uranium dioxide were assessed using four EJ-309 detectors, a mixed field analyser operated in pulse gradient analysis mode, and associated counting components. We observe a background-corrected fast neutron count sensitivity of (2.0 ±â€¯0.3) × 10-4 n g-1 s-1 per detector. This research demonstrates a proof of concept for depleted uranium quantity to be assessed passively on a non-intrusive basis via its spontaneous fission decay.

Gingival overgrowth: Part 2: management strategies.

The effective and predictable management of gingival overgrowth requires correct diagnosis and consideration of aetiological factors, as discussed in Part 1 (BDJ 2017; 222: 85-91). Initial management should involve cause-related therapy, which may resolve or reduce the lesion. If functional, aesthetic and maintenance complications persist following this phase; further treatment may be required in the form of surgery. This paper discusses management strategies, including management of aetiological factors and surgical techniques.

Gingival overgrowth: Part 1: aetiology and clinical diagnosis.

Most commonly, gingival overgrowth is a plaque-induced inflammatory process, which can be modified by systemic disease or medications. However, rare genetic conditions can result in gingival overgrowth with non-plaque-induced aetiology. It is also important to appreciate the potential differential diagnoses of other presentations of enlarged gingival tissues; some may be secondary to localised trauma or non-plaque-induced inflammation and, albeit rarely, others may be manifestations of more sinister diseases or lesions. A definitive diagnosis will then enable an appropriate management strategy. This paper aims to discuss clinical features and diagnoses for conditions presenting with gingival overgrowth and other enlargements of gingival tissues.

Differentiating success from survival in modern implantology--key considerations for case selection, predicting complications and obtaining consent.

The use of dental implants to restore edentulous areas has increased significantly since the 1970s and is now considered, by many, the gold standard restorative treatment. As such it has become increasingly important to understand what constitutes success for these rehabilitations. Increasing focus has been given to acknowledging the difference between success and survival: the two being potentially very different outcomes for such invasive and expensive treatment. This article aims to describe this distinction and ultimately the implications of this for both patient and clinician.

The discrepancy between recommendations and clinical practice for viscosupplementation in osteoarthritis: mind the gap!

Recently AAOS, ACR and OARSI revised their recommendations for the management of knee osteoarthritis (OA) and for hand, knee and hip joints. During ISIAT (International Symposium on Intra-Articular Treatments) 2013 round table on recommendations about the use of intra-articular Hyaluronic Acid (IAHA) in OA, several considerations were elaborated by the ISIAT Technical Expert Panel (TEP) regarding discrepancy between recommendations and clinical practice. The ISIAT TEP gathered the following eight suggestions regarding the drawing of recommendations on the use of IAHA in OA and its comparison with other treatments. It is necessary to merge data coming from both RCTs and registers. Only studies with a strong level of evidence should be taken into account. A common threshold of efficacy should be assessed for comparing treatments. Evaluation of hard outcomes is essential. The effect size of placebo as comparator should be attentively considered in RCTs. Particular attention should be given to different phenotypes of OA that may possibly respond differently to each treatment. Compliance and long-term side effects of different therapeutic approaches should be evaluated. Pharmacoeconomic evaluation should be performed on the long term.

A simple QuEChERS-like extraction approach for molecular chemical characterization of organic aerosols: application to nitrated and oxygenated PAH derivatives (NPAH and OPAH) quantified by GC-NICIMS.

An extraction procedure based on the Quick Easy Cheap Effective Rugged and Safe (QuEChERS) approach has been developed and used for analysis of particle-bound nitrated and oxygenated PAH derivatives (NPAH and OPAH, respectively). Several analytical conditions, for example GC injection temperature and MS detection settings, were optimized. This analytical procedure enabled simultaneous GC-NICIMS quantification of 32 NPAH and 32 OPAH (or other oxygenated compounds), including typical components of secondary organic aerosol (SOA) formed by photooxidation of PAH (e.g. 2-formyl-trans-cinnamaldehyde and 6H-dibenzo[b,d]pyran-6-one). The QuEChERS-like approach was optimized, including the nature of the extraction solvent, the sorbent used for clean-up, and extraction time. The final extraction procedure was based on brief mechanical agitation (vortex mixing for 1.5 min), with 7 mL acetonitrile as solvent. Because dispersive solid-phase extraction (d-SPE) did not provide satisfactory results, SPE using SiO2 was selected for sample purification. Identical results were obtained when the QuEChERS-like and traditional pressurised solvent extraction (PLE) procedures were compared for analysis of fortified ambient air particle samples. The procedure was validated by analysis of two aerosol standard reference materials (NIST SRM 1649b (urban dust) and SRM 2787 (fine particulate matter, <10 µm)). For numerous NPAH and OPAH, this is the first report of their quantification in both SRMs. Compared with other extraction methods, including PLE, the QuEChERS-like procedure resulted in increased productivity and reduced extraction cost. This paper shows that QuEChERS-like extraction procedures can be suitably adapted for molecular chemical characterization of aerosol samples and could be extended to other categories of compound.

[How to handle unexpected biological abnormalities observed in the pre-donation workup for hematopoietic stem cell transplantation: an SFGM-TC report on pre-transplant cytomegalovirus, Epstein-Barr virus, Toxoplasma gondii, or syphilis IgM positive serology test]. / Conduite à tenir devant une anomalie biologique découverte lors du bilan pré-don cellules souches hématopoïétiques: sérologie IgM positive pour le cytomégalovirus, le virus d'Epstein-Barr, la toxoplasmose, ou la syphilis.

In the attempt to harmonize clinical practices between different French transplantation centers, the French Society of Bone Marrow Transplantation and Cell Therapy (SFGM-TC) set up the third annual series of workshops which brought together practitioners from all member centers and took place in October 2012 in Lille. Here we report our results and recommendations regarding the management of pre-transplant donor's cytomegalovirus, Epstein-Barr virus, Toxoplasma gondii, or syphilis IgM positive serology test.

[How to handle unexpected biological abnormalities observed in the pre-donation workup for hematopoietic stem cell transplantation: an SFGM-TC report on pre-transplant positive pregnancy test and monoclonal gammapathy]. / Conduite à tenir devant un problème du donneur de cellules souches hématopoïétiques: test de grossesse positif et gammapathie monoclonale.

In the attempt to harmonize clinical practices between different French transplantation centers, the French Society of Bone Marrow Transplantation and Cell Therapy (SFGM-TC) set up the third annual series of workshops which brought together practitioners from all member centers and took place in October 2012 in Lille. Here we report our results and recommendations regarding the management of common issues related to the donor: pre-transplant pregnancy and monoclonal gammopathy.

The FACT-G7: a rapid version of the functional assessment of cancer therapy-general (FACT-G) for monitoring symptoms and concerns in oncology practice and research.

BACKGROUND: Health-related quality-of-life (HRQOL) assessments in research and clinical oncology settings are increasingly important. HRQOL instruments need to be rapid and still maintain the ability to capture the most relevant patient issues in a valid and reliable manner. The current study develops and validates the FACT-G7, a rapid version of the Functional Assessment of Cancer Therapy-General (FACT-G). PATIENTS AND METHODS: Oncology patients with advanced cancer (N = 533) from 11 diseases sites ranked the symptoms and concerns they viewed as 'the very most important' when undergoing cancer treatment, completed the FACT-G, and additional HRQOL measures. Oncology patients' scores were referenced across a general US population sample (N = 2000). RESULTS: We selected the highest priority cancer-related symptoms and concerns endorsed by patients for inclusion in the FACT-G7. Fatigue and ability to enjoy life were ranked the most highly. The results provide preliminary support for the FACT-G7's internal consistency reliability (α = 0.74) and validity as evidenced by moderate-to-strong relationships with expected criteria. The references for the general population are summarized. CONCLUSIONS: The FACT-G7 can be used to assess top-rated symptoms and concerns for a broad spectrum of advanced cancers in clinical practice and research.

French version of the Functional Assessment of Cancer Therapy-Cognitive Function (FACT-Cog) version 3.

PURPOSE: Impairment of cognitive function, a common complaint in patients receiving chemotherapy, is usually measured through neuropsychological tests. Patient self-evaluation of cognitive difficulties is an important complement to those tests. The Functional Assessment of Cancer Therapy-Cognitive Function (FACT-Cog) is a self-report questionnaire with potential to be used in standard clinical practice as a tool for evaluating patient's cognitive function before, during, and after chemotherapy. The purpose of our study was to conduct linguistic validation of the French version of the FACT-Cog. METHODS: Both qualitative and quantitative methods were used in this study. After undergoing a rigorous translation methodology, the French FACT-Cog version was pretested in France with 35 cancer patients undergoing chemotherapy treatment. Interviews were conducted with all patients to ascertain their understanding of each item. The validation of the final version was conducted among 63 cancer patients, and sociodemographic information was collected as well as brief measure of cognitive function and depression score. RESULTS: Patient comments obtained through the cognitive debriefing interviews indicated that patients understand the French FACT-Cog items as they are intended and that the measure is culturally appropriate. Internal consistency reliability of the subscales, evaluated using Cronbach's coefficient alpha, was high for all four subscales: Perceived Cognitive Impairments = 0.93, Impact On QOL = 0.85, Comments From Others = 0.70, and Perceived Cognitive Abilities = 0.89. All item-total correlations for each subscale were greater than 0.20, and most were greater than 0.50. CONCLUSIONS: Results from this study effectively demonstrate that the French FACT-Cog is a reliable instrument for the self-reporting of cognitive abilities in patients undergoing chemotherapy.

Advanced multiple sclerosis and the psychosocial impact on families.

This study explores family relationships and support needs when adapting to a relative's advanced-multiple sclerosis (MS) around transition into care. A multi-site qualitative study of relatives of people with advanced-MS was conducted. A purposive sample of 25 relatives was selected and interviewed either in the care home or participants' homes. Interviews were recorded, transcribed and analysed using grounded theory methodology and Atlas.ti 5.2 software. Data quality enhancement involved: a self-report questionnaire; triangulation and member-checking. Themes derived from the data were: information, communication and understanding; family relationships, roles and responsibilities; emotions, coping and support; life outlook and reflection. Provision of information and support for families around the transition into care appears to be inconsistent despite there being a need for family members to ask questions and discuss the impact of the condition. Relatives reported that as a family and as individuals they faced significant challenges and were in great need of support at times, but reflected that they would have found it very difficult to accept. Relatives were also often unsure what type of support would have helped. For care providers, there needs to be a shift from the traditional health care professional 'patient-centred' mindset towards more proactive family-centred approaches and steps to encourage this are articulated.

Evaluation of techniques used in the assessment of subtidal epibiotic assemblage structure.

A comparative study was carried out to evaluate the efficiency of a number of techniques commonly used for assessing the structure of subtidal epifaunal communities. Assessments were made of the epifaunal assemblages fouling two substrata: concrete and PVC plastic. Where possible, each technique was undertaken in three ways, namely, in situ underwater, in the laboratory and using image analysis on photographs taken in situ. Comparisons were also made of biomass estimates made on samples taken in situ and in the laboratory. All method and technique combinations assessed detected differences in the epibiotic communities associated with the two fouling substrata. Sampling in situ, in the laboratory and using image analysis gave similar estimates of percent cover. However, there were significant differences in measurements made for most taxa with respect to abundance and frequency counts depending on how the technique was carried out. Laboratory-based sampling of abundance and frequency counts and biomass determinations, rather than in situ or image-analysis based sampling, are recommended for use in future studies of epifaunal fouling.