Publications by authors named "Isabelle Dumont"

26 Publications

  • Page 1 of 1

Feasibility of Percutaneous Bone Biopsy as Part of the Management of Diabetic Foot Osteomyelitis in a 100% Neuropathic, Grade 3 IDSA/IWGDF Population on an Outpatient Basis.

Int J Low Extrem Wounds 2020 Dec 30;19(4):382-387. Epub 2020 Jan 30.

Brugmann University Hospital-Site Victor Horta, Brussels, Belgium.

The present study aimed to evaluate the feasibility of percutaneous bone biopsy in an ambulatory setting as part of the management of diabetic foot osteomyelitis (DFO) on an outpatient basis. DFO may complicate some cases of apparently nonsevere foot infections in patients with diabetes and greatly increase the risk of a lower extremity amputation. It has been suggested that bone culture-based antibiotic therapy is a predictive factor of success in patients with diabetes treated nonsurgically for osteomyelitis of the foot. It is recommended to identify the causative microorganism(s) by the means of either a surgical or percutaneous bone biopsy taken appropriately to select the proper antibiotic therapy. Percutaneous bone biopsy in patients not requiring surgery is, however, not performed in everyday practice as it should be according to the current recommendations. In the present retrospective study, we report a series of 23 consecutive patients with a suspicion of DFO in whom 28 bone samples were collected by percutaneous biopsy at the bedside in an outpatient setting. The percentage of positive cultures was in accordance with that reported in the literature. The mean number of isolates per specimen was 1.04. After a mean 12-month follow-up, the remission was almost of 78%. No adverse event related to the bone biopsy was noted. After a 1-year follow-up, no recurrence was recorded among the patients in remission. The results of the present study suggest that bedside percutaneous bone biopsy performed in the ambulatory setting is a valuable and safe tool in the management of DFO on an outpatient basis.
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http://dx.doi.org/10.1177/1534734620902609DOI Listing
December 2020

Decreasing rates of major lower-extremity amputation in people with diabetes but not in those without: a nationwide study in Belgium.

Diabetologia 2018 09 16;61(9):1966-1977. Epub 2018 Jun 16.

Institute for Health Services Research and Health Economics, German Diabetes Center (DDZ), Leibniz Institute for Diabetes Research at Heinrich Heine University Düsseldorf, Auf'm Hennekamp 65, 40225, Düsseldorf, Germany.

Aims/hypothesis: The reduction of major lower-extremity amputations (LEAs) is one of the main goals in diabetes care. Our aim was to estimate annual LEA rates in individuals with and without diabetes in Belgium, and corresponding time trends.

Methods: Data for 2009-2013 were provided by the Belgian national health insurance funds, covering more than 99% of the Belgian population (about 11 million people). We estimated the age-sex standardised annual amputation rate (first per year) in the populations with and without diabetes for major and minor LEAs, and the corresponding relative risks. To test for time trends, Poisson regression models were fitted.

Results: A total of 5438 individuals (52.1% with diabetes) underwent a major LEA, 2884 people with above- and 3070 with below-the-knee major amputations. A significant decline in the major amputation rate was observed in people with diabetes (2009: 42.3; 2013: 29.9 per 100,000 person-years, 8% annual reduction, p < 0.001), which was particularly evident for major amputations above the knee. The annual major amputation rate remained stable in individuals without diabetes (2009: 6.1 per 100,000 person-years; 2013: 6.0 per 100,000 person-years, p = 0.324) and thus the relative risk reduced from 6.9 to 5.0 (p < 0.001). A significant but weaker decrease was observed for minor amputation in individuals with and without diabetes (5% and 3% annual reduction, respectively, p < 0.001).

Conclusions/interpretation: In this nationwide study, the risk of undergoing a major LEA in Belgium gradually declined for individuals with diabetes between 2009 and 2013. However, continued efforts should be made to further reduce the number of unnecessary amputations.
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http://dx.doi.org/10.1007/s00125-018-4655-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6096627PMC
September 2018

Selling conscience short: a response to Schuklenk and Smalling on conscientious objections by medical professionals.

J Med Ethics 2017 04 28;43(4):241-244. Epub 2016 Sep 28.

School of Social Work, Université du Québec à Montréal, Montreal, Quebec, Canada.

In a thought-provoking paper, Schuklenk and Smalling argue that no right to conscientious objection should be granted to medical professionals. First, they hold that it is impossible to assess either the truth of conscience-based claims or the sincerity of the objectors. Second, even a fettered right to conscientious refusal inevitably has adverse effects on the rights of patients. We argue that the main problem with their position is that it is not derived from a broader reflection on the meaning and implications of freedom of conscience and reasonable accommodation. We point out that they collapse two related but distinct questions, that is, the subjective conception of freedom of conscience and the sincerity test. We note that they do not successfully show that the standard norm according to which exemption claims should not impose undue hardship on others is unworkable. We suggest that the main reason why arguments such as no one is forced to be a medical professional are flawed is that public norms should not constrain citizens to choose between two of their basic rights unless it is necessary. In fine, Schuklenk and Smalling, who see conscience claims as arbitrary dislikes, sell freedom of conscience short and forego any attempts at balancing the competing rights involved. We maintain the authors neglect that most of legal reasoning is contextual and that the blanket restriction of healthcare professionals' freedom of conscience is disproportionate.
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http://dx.doi.org/10.1136/medethics-2016-103903DOI Listing
April 2017

9th GCC closed forum: CAPA in regulated bioanalysis; method robustness, biosimilars, preclinical method validation, endogenous biomarkers, whole blood stability, regulatory audit experiences and electronic laboratory notebooks.

Bioanalysis 2016 Mar 26;8(6):487-95. Epub 2016 Feb 26.

WuXi/XBL, 107 Morgan Lane, Plainsboro, NJ, USA.

The 9th GCCClosed Forum was held just prior to the 2015 Workshop on Recent Issues in Bioanalysis (WRIB) in Miami, FL, USA on 13 April 2015. In attendance were 58 senior-level participants, from eight countries, representing 38 CRO companies offering bioanalytical services. The objective of this meeting was for CRO bioanalytical representatives to meet and discuss scientific and regulatory issues specific to bioanalysis. The issues selected at this year's closed forum include CAPA, biosimilars, preclinical method validation, endogenous biomarkers, whole blood stability, and ELNs. A summary of the industry's best practices and the conclusions from the discussion of these topics is included in this meeting report.
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http://dx.doi.org/10.4155/bio.16.16DOI Listing
March 2016

2014 White Paper on recent issues in bioanalysis: a full immersion in bioanalysis (Part 3 - LBA and immunogenicity).

Bioanalysis 2014 ;6(24):3355-68

Biogen Idec Inc., Cambridge, MA, USA.

The 2014 8th Workshop on Recent Issues in Bioanalysis (8th WRIB), a 5-day full immersion in the evolving field of bioanalysis, took place in Universal City, California, USA. Close to 500 professionals from pharmaceutical and biopharmaceutical companies, contract research organizations and regulatory agencies worldwide convened to share, review, discuss and agree on approaches to address current issues of interest in bioanalysis. The topics covered included both small and large molecules, and involved LCMS, hybrid LBA/LCMS, LBA approaches and immunogenicity. From the prolific discussions held during the workshop, specific recommendations are presented in this 2014 White Paper. As with the previous years' editions, this paper acts as a practical tool to help the bioanalytical community continue advances in scientific excellence, improved quality and better regulatory compliance. Due to its length, the 2014 edition of this comprehensive White Paper has been divided into three parts for editorial reasons. This publication (Part 3) covers the recommendations for Large molecules bioanalysis using LBA and Immunogenicity. Part 1 (Small molecules bioanalysis using LCMS) and Part 2 (Hybrid LBA/LCMS, Electronic Laboratory Notebook and Regulatory Agencies' Input) were published in the Bioanalysis issues 6(22) and 6(23), respectively.
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http://dx.doi.org/10.4155/bio.14.283DOI Listing
August 2015

2014 White Paper on recent issues in bioanalysis: a full immersion in bioanalysis (Part 2 - hybrid LBA/LCMS, ELN & regulatory agencies' input).

Bioanalysis 2014 ;6(23):3237-49

Pfizer, Andover, MA, USA.

The 2014 8th Workshop on Recent Issues in Bioanalysis (8th WRIB), a 5-day full immersion in the evolving field of bioanalysis, took place in Universal City, California, USA. Close to 500 professionals from pharmaceutical and biopharmaceutical companies, contract research organizations and regulatory agencies worldwide convened to share, review, discuss and agree on approaches to address current issues of interest in bioanalysis. The topics covered included both small and large molecules, and involved LCMS, hybrid LBA/LCMS, LBA approaches and immunogenicity. From the prolific discussions held during the workshop, specific recommendations are presented in this 2014 White Paper. As with the previous years' editions, this paper acts as a practical tool to help the bioanalytical community continue advances in scientific excellence, improved quality and better regulatory compliance. Due to its length, the 2014 edition of this comprehensive White Paper has been divided into three parts for editorial reasons. This publication (Part 2) covers the recommendations for Hybrid LBA/LCMS, Electronic Laboratory Notebook and Regulatory Agencies' Input. Part 1 (Small molecules bioanalysis using LCMS) was published in the Bioanalysis issue 6(22) and Part 3 (Large molecules bioanalysis using LBA and Immunogenicity) will be published in the Bioanalysis issue 6(24).
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http://dx.doi.org/10.4155/bio.14.279DOI Listing
August 2015

2014 White Paper on recent issues in bioanalysis: a full immersion in bioanalysis (Part 1--small molecules by LCMS).

Bioanalysis 2014 ;6(22):3039-49

Pfizer, Pearl River, NY, USA.

The 2014 8th Workshop on Recent Issues in Bioanalysis (8th WRIB), a 5-day full immersion in the evolving field of bioanalysis, took place in Universal City, California, USA. Close to 500 professionals from pharmaceutical and biopharmaceutical companies, contract research organizations and regulatory agencies worldwide convened to share, review, discuss and agree on approaches to address current issues of interest in bioanalysis. The topics covered included both small and large molecules, and involved LCMS, hybrid LBA/LCMS, LBA approaches and immunogenicity. From the prolific discussions held during the workshop, specific recommendations are presented in this 2014 White Paper. As with the previous years' editions, this paper acts as a practical tool to help the bioanalytical community continue advances in scientific excellence, improved quality and better regulatory compliance. Due to its length, the 2014 edition of this comprehensive White Paper has been divided into three parts for editorial reasons. This publication (Part 1) covers the recommendations for small molecule bioanalysis using LCMS. Part 2 (Hybrid LBA/LCMS, Electronic Laboratory Notebook and Regulatory Agencies' input) and Part 3 (Large molecules bioanalysis using LBA and Immunogenicity) will be published in the upcoming issues of Bioanalysis.
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http://dx.doi.org/10.4155/bio.14.265DOI Listing
July 2015

8th GCC: consolidated feedback to US FDA on the 2013 draft FDA guidance on bioanalytical method validation.

Bioanalysis 2014 ;6(22):2957-63

Covance Laboratories, Chantilly, VA, USA.

The 8th GCC Closed Forum for Bioanalysis was held in Baltimore, MD, USA on 5 December 2013, immediately following the 2013 AAPS Workshop (Crystal City V): Quantitative Bioanalytical Methods Validation and Implementation--The 2013 Revised FDA Guidance. This GCC meeting was organized to discuss the contents of the draft revised FDA Guidance on bioanalytical method validation that was published in September 2013 and consolidate the feedback of the GCC members. In attendance were 63 senior-level participants, from seven countries, representing 46 bioanalytical CRO companies/sites. This event represented a unique opportunity for CRO bioanalytical experts to share their opinions and concerns regarding the draft FDA Guidance, and to build unified comments to be provided to the FDA.
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http://dx.doi.org/10.4155/bio.14.287DOI Listing
July 2015

Recommendations on incurred sample stability (ISS) by GCC.

Bioanalysis 2014 Sep;6(18):2385-90

Quintiles Bioanalytical & ADME Labs, Ithaca, NY, USA.

The topic of incurred sample stability (ISS) has generated considerable discussion within the bioanalytical community in recent years. The subject was an integral part of the seventh annual Workshop on Recent Issues in Bioanalysis (WRIB) held in Long Beach, CA, USA, in April 2013, and at the Global CRO Council for Bioanalysis (GCC) meeting preceding it. Discussion at both events focused on the use of incurred samples for ISS purposes in light of results from a recent GCC survey completed by member companies. This paper reports the consensus resulting from these discussions and serves as a useful reference for depicting ISS issues and concerns, summarizing the GCC survey results and providing helpful recommendations on ISS in the context of bioanalytical method development and application.
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http://dx.doi.org/10.4155/bio.14.155DOI Listing
September 2014

Choosing the appropriate matrix to perform a scientifically meaningful lipemic plasma test in bioanalytical method validation.

Bioanalysis 2014 12;6(12):1639-46. Epub 2014 Mar 12.

Algorithme Pharma Inc., Laval, Montreal, Quebec, Canada.

Laurence Mayrand-Provencher has obtained a Master of Science in Chemistry from Université de Montréal. With over 3 years of experience as a scientist in the bioanalysis industry, he is now a scientist in method development at Algorithme Pharma. His experiences have led him to conduct robust and effective method development of bioanalytical assays, specifically in the LC-MS/MS field. Many regulatory agencies include in their guidelines the need to investigate the effect of lipemic plasma on the reliability of the data as part of a bioanalytical assay validation. Lipids can cause matrix effect, specificity and recovery issues, which can potentially lead to inaccurate data if left unaccounted for. However, finding the appropriate matrix type to be used to perform a lipemic plasma test is a major challenge, as the differences between those commercially available are not well known. The work reported herein describes the differences in lipid content between normal plasma, synthetic lipemic plasma mixes, and two types of natural lipemic plasma. The results obtained show that natural plasma with high triglycerides content should be used to perform a scientifically meaningful lipemic plasma test.
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http://dx.doi.org/10.4155/bio.14.33DOI Listing
March 2015

Implementation of a quality improvement initiative in Belgian diabetic foot clinics: feasibility and initial results.

Diabetes Metab Res Rev 2014 Jul;30(5):435-43

Background: This article aims to describe the implementation and initial results of an audit-feedback quality improvement initiative in Belgian diabetic foot clinics.

Methods: Using self-developed software and questionnaires, diabetic foot clinics collected data in 2005, 2008 and 2011, covering characteristics, history and ulcer severity, management and outcome of the first 52 patients presenting with a Wagner grade ≥ 2 diabetic foot ulcer or acute neuropathic osteoarthropathy that year. Quality improvement was encouraged by meetings and by anonymous benchmarking of diabetic foot clinics.

Results: The first audit-feedback cycle was a pilot study. Subsequent audits, with a modified methodology, had increasing rates of participation and data completeness. Over 85% of diabetic foot clinics participated and 3372 unique patients were sampled between 2005 and 2011 (3312 with a diabetic foot ulcer and 111 with acute neuropathic osteoarthropathy). Median age was 70 years, median diabetes duration was 14 years and 64% were men. Of all diabetic foot ulcers, 51% were plantar and 29% were both ischaemic and deeply infected. Ulcer healing rate at 6 months significantly increased from 49% to 54% between 2008 and 2011. Management of diabetic foot ulcers varied between diabetic foot clinics: 88% of plantar mid-foot ulcers were off-loaded (P10-P90: 64-100%), and 42% of ischaemic limbs were revascularized (P10-P90: 22-69%) in 2011.

Conclusions: A unique, nationwide quality improvement initiative was established among diabetic foot clinics, covering ulcer healing, lower limb amputation and many other aspects of diabetic foot care. Data completeness increased, thanks in part to questionnaire revision. Benchmarking remains challenging, given the many possible indicators and limited sample size. The optimized questionnaire allows future quality of care monitoring in diabetic foot clinics.
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http://dx.doi.org/10.1002/dmrr.2524DOI Listing
July 2014

2013 White Paper on recent issues in bioanalysis: 'hybrid'--the best of LBA and LCMS.

Bioanalysis 2013 Dec 10;5(23):2903-18. Epub 2013 Oct 10.

Biogen Idec Inc.,Cambridge, MA, USA.

The 2013 7th Workshop on Recent Issues in Bioanalysis was held in Long Beach, California, USA, where close to 500 professionals from pharmaceutical and biopharmaceutical companies, CROs and regulatory agencies convened to discuss current topics of interest in bioanalysis. These 'hot' topics, which covered both small and large molecules, were the starting point for fruitful exchanges of knowledge, and sharing of ideas among speakers, panelists and attendees. The discussions led to specific recommendations pertinent to bioanalytical science. Such as the previous editions, this 2013 White Paper addresses important bioanalytical issues and provides practical answers to the topics presented, discussed and agreed upon by the global bioanalytical community attending the 7th Workshop on Recent Issues in Bioanalysis.
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http://dx.doi.org/10.4155/bio.13.238DOI Listing
December 2013

2012 white paper on recent issues in bioanalysis and alignment of multiple guidelines.

Bioanalysis 2012 Sep;4(18):2213-26

Bristol-Myers Squibb, Princeton, NJ, USA.

Over 400 professionals representing pharmaceutical companies, CROs, and multiple regulatory agencies participated in the 6th Workshop on Recent Issues in Bioanalysis (WRIB). Like the previous sessions, this event was in the format of a practical, focused, highly interactive and informative workshop aiming for high-quality, improved regulatory compliance and scientific excellence. Numerous 'hot' topics in bioanalysis of both small and large molecules were shared and discussed, leading to consensus and recommendations among panelists and attendees representing the bioanalytical community. The major outcome of this year's workshop was the noticeable alignment of multiple bioanalytical guidance/guidelines from different regulatory agencies. This represents a concrete step forward in the global harmonization of bioanalytical activities. The present 2012 White Paper acts as a practical and useful reference document that provides key information and solutions on several topics and issues in the constantly evolving world of bioanalysis.
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http://dx.doi.org/10.4155/bio.12.205DOI Listing
September 2012

Recommendations on bioanalytical method stability implications of co-administered and co-formulated drugs by Global CRO Council for Bioanalysis (GCC).

Bioanalysis 2012 Sep;4(17):2117-26

Advion Bioanalytical Laboratories, Quintiles, NY, USA.

An open letter written by the Global CRO Council for Bioanalysis (GCC) describing the GCC survey results on stability data from co-administered and co-formulated drugs was sent to multiple regulatory authorities on 14 December 2011. This letter and further discussions at different GCC meetings led to subsequent recommendations on this topic of widespread interest within the bioanalytical community over the past 2 years.
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http://dx.doi.org/10.4155/bio.12.192DOI Listing
September 2012

2011 White paper on recent issues in bioanalysis and regulatory findings from audits and inspections.

Bioanalysis 2011 Sep;3(18):2081-96

Algorithme Pharma Inc., Laval (Montreal) Quebec, H7V 4B3, Canada.

The 5th Workshop on Recent Issues in Bioanalysis (WRIB) was organized by the Calibration and Validation Group as a 2-day full immersion workshop for pharmaceutical companies, CROs and regulatory agencies to discuss, review, share perspectives, provide potential solutions and agree upon a consistent approach to recent issues in the bioanalysis of both small and large molecules. High quality, better compliance to regulations and scientific excellence are the foundation of this workshop. As in the previous editions of this significant event, recommendations were made and a consensus was reached among panelists and attendees, including industry leaders and regulatory experts representing the global bioanalytical community, on many 'hot' topics in bioanalysis. This 2011 White Paper is based on the conclusions from this workshop, and aims to provide a practical reference guide on those topics.
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http://dx.doi.org/10.4155/bio.11.192DOI Listing
September 2011

Impact of oxcarbazepine sulfate metabolite on incurred sample reanalysis and quantification of oxcarbazepine.

Bioanalysis 2011 May;3(9):973-82

Algorithme Pharma Inc., 575 Armand Frappier, Laval, Quebec, Canada.

Background: Recently, incurred sample reanalysis (ISR) has become a requirement in bioanalysis. The general guidance recommends investigating ISR failure to evaluate the suitability of an analytical method. In the case of acceptable ISR evaluation, there were no precise recommendations for further testing when sporadic values were obtained.

Results: The ISR evaluation performed during a bioequivalence study for the anticonvulsant drug oxcarbazepine showed acceptable ISR results, but one particular chromatographic anomaly led to a thorough investigation. The finding of these tests showed that an oxcarbazepine phase II metabolite occasionally co-eluted with the drug and impacted oxcarbazepine's quantitation through in-source conversion.

Conclusion: This paper demonstrates the necessity of rigorous interpretation of ISR results and close monitoring of all subject sample results.
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http://dx.doi.org/10.4155/bio.11.54DOI Listing
May 2011

Techniques for framing questions in conducting family meetings in palliative care.

Palliat Support Care 2009 Jun;7(2):163-70

Department of Psychiatry and Behavioral Sciences, Memorial Sloan-Kettering Cancer Center, New York, New York, USA.

Objective: Family therapy has developed several approaches to framing questions within family meetings, but few of these techniques have been adapted for palliative care. We focus on the application of questioning techniques from systemic family therapy to palliative care. More specifically, we describe and give examples of the model of asking questions developed by Karl Tomm (1988) through its application in Family Focused Grief Therapy (FFGT), a preventive intervention delivered to high-risk families during palliative care and bereavement.

Methods: First, the type of questions used across the course of therapy is explored based on the interventive questioning model. Then, a case example is provided to demonstrate the use and adaptation of this model in a palliative care setting.

Results: At the beginning of therapy, the most frequent questions were linear and circular, moving around the family to build up a picture of events from everyone's perspective. As for the frequency of reflexive and strategic questions, these increased as the therapy progressed, bringing the family to new perspectives. The case example fleshes out the importance of each type of question, all of which have a proper place in the course of therapy.

Significance Of Results: These illustrations highlight the value of having a model of questioning styles to guide the clinician when exploring palliative care issues, such as care provision, coping and grief, intimacy, and discussing death. This framework could be useful in guiding supervisors, trainees, and clinicians seeking to build skills and optimize their interventions in a palliative care setting.
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http://dx.doi.org/10.1017/S1478951509000212DOI Listing
June 2009

Diagnosis and prevalence of onychomycosis in diabetic neuropathic patients: an observational study.

J Am Podiatr Med Assoc 2009 Mar-Apr;99(2):135-9

Vésale Hospital, Montigny-le-Tilleul, Belgium; Foot Center, Ransart, Belgium; 36 rue du Melon, 1190 Bruxelles, Belgium.

Background: An observational study was conducted to assess the prevalence of onychomycosis in clinically suspected diabetic neuropathic patients and to assess the reliability of the diagnosis.

Methods: One hundred successive type 1 and 2 diabetic patients with diabetic neuropathy were followed. Diabetic neuropathy was defined by a vibration perception threshold greater than 25 V and onychomycosis by clinical diagnosis. Samples of the most affected nail were taken. Potassium hydroxide testing and culture were performed. Photographs of the nails were used by two dermatologists for diagnosis.

Results: The mean +/- SE age was 62.3 +/- 11.4 years for the 20 onychomycotic patients and 60.3 +/- 10.4 years for the entire cohort; 14 onychomycotic patients (70%) were male versus 56 in the full cohort (56%) (P < .05). The prevalence of onychomycosis was 20% (culture and potassium hydroxide test positive) and 24% (culture positive). Twenty or 30 patients were positive by the potassium hydroxide test, depending on the investigator. The most frequent pathogen found was Trichophyton rubrum (11 of 20 patients; 55%). The positive predictive values of the dermatologist's diagnoses were 57.8% and 35.6%, and the negative predictive values were 85.0% and 90.5%. The two expert's results were significantly different (P < .05).

Conclusions: The diagnosis of onychomycosis is difficult to make. The diagnostic methods commonly used are not satisfactory. If onychomycosis is dangerous for the diabetic foot, a better diagnostic method is needed.
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http://dx.doi.org/10.7547/0980135DOI Listing
June 2009

End-of-life care and the grieving process: family caregivers who have experienced the loss of a terminal-phase cancer patient.

Qual Health Res 2008 Aug;18(8):1049-61

Department of Psychiatry and Behavioral Sciences, Memorial Sloan-Kettering Cancer Center, New York, New York, USA.

Family caregivers of a loved one with advanced cancer are at risk for developing bereavement complications following the loss of the person they cared for. However, little research has studied caregiving and bereavement experiences as an ongoing process. This study was conducted with the aim of identifying the main elements constitutive of the experience of providing care and assistance to a patient with terminal cancer that influence the grieving process. This qualitative study, conducted among 18 family caregivers, led to the specification of six principal dimensions of the caregiving experience: characteristics of the family caregiver and of the patient, symptoms of the illness, the relational context, social and professional support, and circumstances surrounding the death. Among these dimensions, the constituent elements of the caregiving experience that might positively or negatively influence the grieving process were identified. This knowledge is useful for a more perspicuous identification of caregivers who might experience bereavement complications.
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http://dx.doi.org/10.1177/1049732308320110DOI Listing
August 2008

Continuity of care for advanced cancer patients.

J Palliat Care 2005 ;21(1):49-56

Ecole de service social, Université Laval, Centre de recherche de I'Hôtel-Dieu de Québec, Equipe de recherche de la Maison Michel-Sarrazin, CHUQ, Canada.

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June 2005

Regulation of eNOS expression in brain endothelial cells by perinuclear EP(3) receptors.

Circ Res 2002 Apr;90(6):682-9

Departments of Pediatrics, Research Center of Hôpital Sainte-Justine, Montréal.

We reported upregulation of endothelial nitric oxide synthase (eNOS) by PGE(2) in tissues and presence of perinuclear PGE(2) receptors (EP). We presently studied mechanisms by which PGE(2) induces eNOS expression in cerebral microvessel endothelial cells (ECs). 16,16-Dimethyl PGE(2) and selective EP(3) receptor agonist M&B28767 increased eNOS expression in ECs and the NO-dependent vasorelaxant responses induced by substance P on cerebral microvessels. These effects could be prevented by prostaglandin transporter blocker bromcresol green and actinomycin D. EP(3) immunoreactivity was confirmed on plasma and perinuclear membrane of ECs. M&B28767 increased eNOS RNA expression in EC nuclei, and this effect was augmented by overexpression of EP(3) receptors. M&B28767 also induced increased phosphorylation of Erk-1/2 and Akt, as well as changes in membrane potential revealed by the potentiometric fluorescent dye RH421, which were prevented by iberiotoxin; perinuclear K(Ca) channels were detected, and their functionality corroborated by NS1619-induced Ca(2+) signals and nuclear membrane potential changes. Moreover, pertussis toxin, Ca(2+) chelator, and channel blockers EGTA, BAPTA, and SK&F96365, as well as K(Ca) channel blocker iberiotoxin, protein-kinase inhibitors wortmannin and PD 98059, and NF-kappaB inhibitor pyrrolidine dithiocarbamate prevented M&B28767-induced increase in Ca(2+) transients and/or eNOS expression in EC nuclei. We describe for the first time that PGE(2) through its access into cell by prostaglandin transporters induces eNOS expression by activating perinuclear EP(3) receptors coupled to pertussis toxin-sensitive G proteins, a process that depends on nuclear envelope K(Ca) channels, protein kinases, and NF-kappaB; the roles for nuclear EP(3) receptors seem different from those on plasma membrane.
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http://dx.doi.org/10.1161/01.res.0000013303.17964.7aDOI Listing
April 2002