967 resultados para Robust methods
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NICaN Regional Supportive & Palliative Care Network Friday 30th May 2008 Lecture Theatre, Fern House Antrim 2.00 pm - 5.00 pm Welcome, Introductions Stuart MacDonnell, Chair of the Supportive and Palliative Care network welcomed everyone to the meeting. This meeting had been rescheduled to accommodate the validation workshop for the regional palliative care model, which took place on Friday,18th April. Acknowledging the full agenda, several items were pulled forward to accommodate speakers SPC_0809_03 Modernisation and Reform of Supportive and Palliative care Mr MacDonnell welcomed Dr Sonja McIlfatrick and Dr Donna Fitzimons, members of the Phase 1 Project Team for the Modernisation and Reform of palliative care. Their presentation highlighted the journey taken by the Project Team since January 2008 - May 2008. Seeking to deliver the network vision, for any person with palliative care need, cancer or non - cancer, the project team incorporated several methodologies. The literature review identified best practice. An assessment of need including epidemiological data and review of service provision. Consultation reflected the engagement with patients, carers and professional forums, primary care and non-malignant focus groups. The breadth of consultation confirmed the evidence for the identified components of the model. These were validated at the April workshop. External review of the work was provided by Dr Phil Larkin (Galway Uni) Prof David Clark (End of Life Care Observatory, Lancaster University) and Mr Bob Neillans (Chair of the Mid Trent Palliative care network, which has been involved in the Delivering choice programme within Lincolnshire). The Guiding Principles of the model reinforced Patient and family centred care, enhanced community provision and supported by specialists. The components of the model are · Identification of patient with Palliative careened · Holistic Assessment · Integration of services · Coordination of care · End of Life Care and Bereavement Care The consultation process also highlighted the need for Increased Public and Professional Awareness. This was recognised as an encompassing component. Underpinning the model is the need for robust Education and common core values e.g. dignity, choice, advocacy, empowerment, partnership working. Stuart MacDonnell, who also chaired the steering group during the project, congratulated the Project Team for delivering the comprehensive document on schedule. The Report has been submitted to the NICaN Board and the DHSSPSNI. In addition, an outline for Phase 2 of this work has been submitted. Mr MacDonnell recognised that there is real opportunity for palliative care to benefit from the DHSSPSNI commitment to concrete developments. Phase 2 will progress the current high-level components of the model into quality services developments at a local level, demonstrating integration throughout. The methods propose continued engagement with the Delivering Choice Programme enabled through a Central and also Local Teams. The report and the Appendices care available on the NICaN website www.nican@n-i.nhs.uk SPC_0809_01 Chairman's Business · Update on the Cancer Service Framework, the document has been submitted and presented to the Departmental Programme Board. Next stages will include the review of costs and development of a implementation guidance It is hoped that the completed document should be available for public consultation in Autumn 2008. with a launch of the framework document and accompanying implementation guide in Spring 2009. Some funding has already been identified to advance key areas of work including, Advanced communication skills training, peer review and an appointment of a post to develop the cancerni.net, focusing on children and e-learning tools. · Children's and Adolescent Cancer network group , Liz Henderson is to convene a group to consider how this is to be taken forward. · NICaN appointments Recognition was given to the significant contribution made by Dr Gerard Daly during his position as NICaN Lead Clinician, particularly throughout the early establishment of the NICaN. Dr Dermott Hughes (Western Trust) has been appointed as the NICaN Medical Director. The Primary Care Director post has been advertised and it is hoped that the Director of Network will be advertised later in Summer. Endorsement of End of Life care paper. The Paper was presented and endorsed at the March 2008 NICaN Board meeting. Mr David Galloway (Director of Secondary Care) emphasised the need for this important work to be recognised within the regional model to ensure that it is reflected in future models of service delivery Congratulations were again echoed to the Chair of the End of Life Group for this work, Dr Glynis Henry, and the working group Other recognition Mr MacDonnell congratulated the significant achievements across the network. These include: · Dr Francis Robinson (Consultant Palliative Medicine, Western Trust) Awarded - Consultant of the year at the NI Health Care awards. · Mrs Evelyn Whittaker Hospice Nurse Specialist, NI Hospice, Joint Second Prize in the Development award within the International Journal of Palliative Nursing Awards, for her work in development of palliative care education in nursing homes. · Mr Ray Elder is the newly appointed Team Leader of Community Palliative care, SE Trust. · Mrs Bridget Denvir, who managed the establishment of one of the first community multiprofessional palliative care teams is moving to work with establishing integrated teams within the Belfast Trust. Bridget has been an active core member of the network and here contribution has been much appreciated. Mrs Sharon Barr will attend in future. SPC_0809_02 Minutes & matters Arising from Meeting, 13th December 2007 No amendments were made to the draft minutes from the December meeting. These will be posted on the NICaN website for future reference. Palliative Care Research Following consultation, the response to the business case for the All Ireland Institute was forwarded on 22 February 2008 to Prof David Clark. Prof Judith Hill informed the group that terms of tender are now being developed. Awareness raising across academic institutions continues to engage interest in potential partnerships. Atlantic Philantrophies have offered financial support to the venture and match funding is being sought from across jurisdictions. Previous discussions at Network meetings have endorsed the need to establish a work strand for research and development within palliative and end of life care. To identify the body of interested parties and explore the strengths and weaknesses of a collaborative model for research, a workshop, - Building collaboration for Palliative and End of life Care Research -will take place on 4 June 10am - 2pm.in the Comfort Hotel.Antrim, The workshop will be chaired by Prof David Clark, Director of the International Observatory on End of Life Care. Prof Shelia Payne, Help the Hospices Chair in Hospice Studies and co director of the Cancer Experiences Collaborative will present the Experiences and Results from Research Collaborative. Feedback from this event will be brought back to the next meeting in September. SPC_0809_04 Patient Information pathways - a pathway for advanced disease Ms Danny Sinclair, NICaN Regional Coordinator for Patient Information informed the network of how patient information pathways have been developed in line with the Cancer Services Collaborative. Emerging themes, with regard to information needs of patients with advanced disease, are being identified from the work undertaken across the tumour groups. It is important to identify all information needs to develop a generic pathway of information resources for advanced disease to be endorsed by the Supportive and Palliative care network. This could be used across the all tumour specific information pathways and across organisational boundaries. The resulting pathway could potentially be used for non- cancer condition. A group is to be established to take this work forward. The group will: · Develop a list of advanced disease information themes · .Identify when they become relevant for the patient or their carer · .Identify existing resources · .Develop resources where needed · .Participate or nominate when review is required Dr Sheila Kelly nominated Helen Hume (SETrust) Paula Kealey will also contribute to this work; a nomination from the Patient and Public Information Forum has also been identified. A date will be circulated across the network to engage further interest and establish group SPC_0809_08 Development of a Regional Syringe Driver Prescription Chart Ms Kathy Stephenson reported that the second consultation of the draft regional syringe driver prescription chart and the focus group discussions, Pilots of the chart are to be undertaken within Trust, Hospices and General Practices. SPC_0809_05 A framework for Generalist and Specialist Palliative and End of Life Care Competency Dr Kathleen Dunne, lead of the Education works strand, reported on the findings following consultation of the Education framework. The report was widely appreciated across the network and valued as a significant and timely document for the commissioning of generalist and specialist adult palliative care education. Mr MacDonnell congratulated Dr Dunne and the members of the education workstrand for developing the framework aligning its significance to the underpinning needs of the regional model Amendments will be made to the document and then forwarded to the NICaN Board for endorsement. A process of implementation will be explored and reported to the network group at the September meeting. Key target areas for generalist palliative care education were highlighted within care of the elderly and general medicine. . SPC_0809_06 Pallcareni.net-a website for people with palliative care needs Ms Danny Sinclair, reminded the group of the pending amalgamation of the CAPriCORN and NICaN website. The resulting new web address will be www. cancerni.net. Recurrent funding has been secured to ensure the development of the supportive and palliative care website.www.Pallcareni.net The new website will host good information for people with palliative care needs, regardless of diagnosis. It will be accessible via the cancerni.net portal or independently as the pallcareni portal. It will signpost people with palliative care needs to condition- specific websites. The website will also enable the communication needs of the NI Regional Supportive & Palliative Care Network. This is a very significant method of seeking to enable greater understanding of palliative care for public and professionals, as highlighted within the regional model. Currently the material from the CAPriCORN website is being migrated onto cancerni and /or pallcareni.net as appropriate. To enable the further development of this opportunity a steering group of interested individuals is to be established. Their role will be to: · Drive the development of the website so it meets the needs of public and professionals through the sourcing and development of additional content · Identify any support that is needed, e.g. technical support · Review the website as a whole as it grows (coordinating condition-specific developments) · Review the functions of the website to aid communication throughout the Supportive and Palliative care network The steering group representation should reflect the constituencies within the Supportive and Palliative Care network. Current expressions of interest have come from Heather Reid and Valerie Peacock. A date will be circulated across the network to engage further interest and establish group SPC_0809_07 Update of Guidelines workstrand Dr Pauline Wilkinson presented the current work within the guidelines workstrand. 1. Brief Holistic Assessment & Referral Criteria to Specialist Palliative Care The development of an Holistic assessment Tool will help to identify holistic need at generalist and specialist level. Recognition of complex need prompts appropriate referral to specialist palliative care. The regional referral form is compatible with the Minimum Data set. The final drafts of this work are to be circulated widely, inclusive of service framework groups, primary care, secondary care and the supportive and palliative care network. Consultation will take place during June and July. Piloting of the forms will also be undertaken. 2. Control of Pain in Cancer Patients The original guidelines where developed 2003 and are now ready for review. The Mapping exercise, undertaken in May 2007, highlighted that the Guidelines were poorly adopted. The group have reviewed the pending SIGN 2 guidelines for pain with regard to practice in Northern Ireland. These are highly evidence based and are due to be launched this Summer. Whilst an excellent resource their comprehensiveness limits their readability, this may result in poor compliance. The Guidelines group feel it is important to have accessible and user-friendly guidelines particularly for Generalists and Out of hours. There are examples of good work that has taken place across the province, but there is a need for regional consistency. Dr Wilkinson has contacted Dr Carolyn Harper (Deputy CMO) and GAIN with regard to enabling funding to progress this work. The Guidelines group hope to approach the NICaN Primary Care Group to work in collaboratively on this piece, based on the templates already available. The works should be available in both electronic and paper versions. 3. Care of the dying & Breaking bad news Dr Gail Johnston has now completed an Audit of the Care of the Dying Pathways within the EHSSB. Gail is also seeking to examine to what extent the Regional Guidelines for Breaking Bad News are being implemented in the EHSSB with a view to identifying the need for further training or organisational structures that would facilitate future uptake. 4. Advances in new Technology Syringe Drivers Dr Wilkinson reported on a presentation made to the guidelines group by Mr Jim Elliot, Principle Engineer, Cardiology & Ann McLean, and Macmillan Palliative Care Nurse RVH. There is increasing concern with regard to how devices meet the recommended safety standards and how to reduce error. New devices have 3 point checking, automatic detection of syringe, automatic flow rates, full range of alarms, battery status and data download to provide an event log. There are now 2 companies in UK who have devices that meet these safety criteria. The current Graseby syringe drivers, which have been on the market and used predominately within Northern Ireland over the past 27 years Most new devices are not compatible with the regionally available monoject syringe, however contractual changes will lead to the withdrawal of the monoject syringes in October 2008. The Guidelines group supports a regional approach to this matter. This was echoed in the Supportive and Palliative care network. An option appraisal, identifying costs, and training issues should be developed through the engagement with Trusts and DHSSPSNI. The issue of Patient safety should be raised with the DHSSPSNI. SPC_0809_09 Evaluation of Supportive and Palliative Care network Deferred to next meeting. . SPC_0809_10 Emerging Issues Mrs Anne Coyle, Bereavement Coordinator, Southern Trust, announced that the Regional Bereavement Strategy is soon to be released. Anne supported the close alignment between the content of the strategy and the work of the regional model and other workstrands within the Supportive and Palliative care network. Ms Eleanor Donaghy, Transplant Coordinator, briefly highlighted the issue of tissue donation. Each year Northern Ireland has a dearth of corneal donations. There is no upper age limit for donation and retrieval is not limited by a cancer diagnosis. Recipients do not require immunosuppressive and the transplant is lifelong. The National Blood Service provided coordination of this donation they may be contacted via 07659180773. It is hoped that Mrs Coyle and Ms Donaghy could provide more comprehensive presentations at a future meeting. Events · Irish Psycho- Oncology Group Seminar, Cork 6 June, Exploring the Struggle for meaning in Cancer · Integrated Care: Putting Research into Practice, 13June, Trinity College, Dublin · Macmillan online conference Friday 13 June 2008, 9am - 5pm · Delivering effective end of life care: developing partnership working 15 Oct 2008, 9.30 -4.15 pm London Network Meeting was closed at 5.00pm SPC_0607_ Dates of Future Meetings (please note the change of venue) 10th September 2008, 1.30 - 5pm venue to be decided15th January 2009, 1.30 - 5pm venue to be decided12th May 2009, 1.30 - 5pm venue to be decided Attendances Apologies Stuart MacDonnellLorna NevinSonja McIlfatrick Donna FitzsimonsKathleen DunnePauline WilkinsonKathy StephensonSheila KellyMarie Nugent,Anne CoyleFiona GilmourJudith HillLorna DicksonMargaret CarlinLoretta GribbenYvonne Duff Lesley NelsonLiz HendersonSue FosterCathy PayneGraeme PaynePatricia MageeGeraldine WeatherupPaula KealyCaroline McAfeeLinda WrayValerie PeacockAnn McCleanRay Elder Martin BradleyHelen HumeGillian RankinHeather MonteverdeJulie DoyleAlison PorterYvonne SmythLiz Atkinson,Glynis HenryMaeve HullyCaroline HughesAnn FinnBob BrownSharon BarrJulie DoyleJanis McCulla .
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Bacteria can survive on hospital textiles and surfaces, from which they can be disseminated, representing a source of health care-associated infections (HCAIs). Surfaces containing copper (Cu), which is known for its bactericidal properties, could be an efficient way to lower the burden of potential pathogens. The antimicrobial activity of Cu-sputtered polyester surfaces, obtained by direct-current magnetron sputtering (DCMS), against methicillin-resistant Staphylococcus aureus (MRSA) was tested. The Cu-polyester microstructure was characterized by high-resolution transmission electron microscopy to determine the microstructure of the Cu nanoparticles and by profilometry to assess the thickness of the layers. Sputtering at 300 mA for 160 s led to a Cu film thickness of 20 nm (100 Cu layers) containing 0.209% (wt/wt) polyester. The viability of MRSA strain ATCC 43300 on Cu-sputtered polyester was evaluated by four methods: (i) mechanical detachment, (ii) microcalorimetry, (iii) direct transfer onto plates, and (iv) stereomicroscopy. The low efficacy of mechanical detachment impeded bacterial viability estimations. Microcalorimetry provided only semiquantitative results. Direct transfer onto plates and stereomicroscopy seemed to be the most suitable methods to evaluate the bacterial inactivation potential of Cu-sputtered polyester surfaces, since they presented the least experimental bias. Cu-polyester samples sputtered for 160 s by DCMS were further tested against 10 clinical MRSA isolates and showed a high level of bactericidal activity, with a 4-log(10) reduction in the initial MRSA load (10(6) CFU) within 1 h. Cu-sputtered polyester surfaces might be of use to prevent the transmission of HCAI pathogens.
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A field survey on schistosomiais was carried out in 1998, in the municipality of Pedro de Toledo, a low endemic area in the state of São Paulo, Brazil. According to the parasitologic Kato-Katz method, the prevalence rate was 1.6%, with an infection intensity of 40.9 eggs per gram of stool. By the immunofluorescence test (IFT) for detection of IgG and IgM antibodies in the serum, IgG-IFT and IgM-IFT, respectively, prevalence indices of 33.2% and 33.5% were observed. To assess the impact of the schistosomiasis control program in the area, parasitologic and serologic data obtained in 1998, analyzed according to the age, sex, and residence zone, were compared to previous data obtained in a epidemiologic study carried out in 1980, when prevalence indices were of 22.8% and 55.5%, respectively by Kato-Katz and IgG-IFT. A significant fall of the prevalence was observed, indicating that the control measures were effective. Nonetheless, residual transmission was observed, demonstrating the need for a joint effort to include new approaches for better understanding the real situation and improving the control of the disease in low endemic areas.
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The aim of this study was to evaluate the use of one of the molecular typing methods such as PCR (polymerase chain reaction) following by RFLP (restriction fragment length polymorphism) analysis in the identification of Candida species and then to differentiate the identified azole susceptible and resistant Candida albicans strains by using AP-PCR (arbitrarily primed-polymerase chain reaction). The identification of Candida species by PCR and RFLP analysis was based on the size and primary structural variation of rDNA intergenic spacer regions (ITS). Forty-four clinical Candida isolates comprising 5 species were included to the study. The amplification products were digested individually with 3 different restriction enzymes: HaeIII, DdeI, and BfaI. All the isolates tested yielded the expected band patterns by PCR and RFLP analysis. The results obtained from this study demonstrate that Candida species can be differentiated as C. albicans and non-C. albicans strains only by using HaeIII restriction enzyme and BfaI maintains the differentiation of these non-C. albicans species. After identification Candida species with RFLP analysis, C. albicans strains were included to the AP-PCR test. By using AP-PCR, fluconazole susceptible and resistant strains were differentiated. Nine fluconazole susceptible and 24 fluconazole resistant C. albicans were included to the study. Fluconazole resistant strains had more bands when evaluating with the agarose gel electrophoresis but there were no specific discriminatory band patterns to warrant the differentiation of the resistance. The identification of Candida species with the amplification of intergenic spacer region and RFLP analysis is a practical, short, and a reliable method when comparing to the conventional time-consuming Candida species identification methods. The fluconazole susceptibility testing with AP-PCR seems to be a promising method but further studies must be performed for more specific results.
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Four methods (chromogenic, acidimetric, inhibition, and iodometric) for demonstration of the beta-lactamase production by 70 isolates of Neisseria gonorrhoeae, were evaluated in Cuba. There was 100% correlation between all beta-lactamase methods and the standardized penicillin dilution susceptibility test for penicillinase-non-producing N. gonorrhoeae. For penicillinase-producing N. gonorrhoeae strains, there was a perfect correlation between the chromogenic method and penicillin susceptibility testing, but one and two strains failed to give a positive result for beta-lactamase with the inhibition/acidimetric and the iodometric methods, respectively. There was a high concordance between the chromogenic method, considered as gold standard and the rest of penicillinase tests evaluated: Kappa Index (KI) = 0.98 for inhibition/acidimetric methods and KI = 0.97 for the iodometric method. The four methods evaluated were accurate, reproducible, easily readable, economical, and ease to use for screening primary isolates of N. gonorrhoeae in Cuba. We recommended the use of the inhibition method, when testing the penicillinase activity in gonococcal isolates in provincial and municipal reference laboratories.
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We extend PML theory to account for information on the conditional moments up to order four, but without assuming a parametric model, to avoid a risk of misspecification of the conditional distribution. The key statistical tool is the quartic exponential family, which allows us to generalize the PML2 and QGPML1 methods proposed in Gourieroux et al. (1984) to PML4 and QGPML2 methods, respectively. An asymptotic theory is developed. The key numerical tool that we use is the Gauss-Freud integration scheme that solves a computational problem that has previously been raised in several fields. Simulation exercises demonstrate the feasibility and robustness of the methods [Authors]
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Mycobacterium tuberculosis strains resistant to streptomycin (SM), isoniazid (INH), and/or rifampin (RIF) as determined by the conventional Löwenstein-Jensen proportion method (LJPM) were compared with the E test, a minimum inhibitory concentration susceptibility method. Discrepant isolates were further evaluated by BACTEC and by DNA sequence analyses for mutations in genes most often associated with resistance to these drugs (rpsL, katG, inhA, and rpoB). Preliminary discordant E test results were seen in 75% of isolates resistant to SM and in 11% to INH. Discordance improved for these two drugs (63%) for SM and none for INH when isolates were re-tested but worsened for RIF (30%). Despite good agreement between phenotypic results and sequencing analyses, wild type profiles were detected on resistant strains mainly for SM and INH. It should be aware that susceptible isolates according to molecular methods might contain other mechanisms of resistance. Although reproducibility of the LJPM susceptibility method has been established, variable E test results for some M. tuberculosis isolates poses questions regarding its reproducibility particularly the impact of E test performance which may vary among laboratories despite adherence to recommended protocols. Further studies must be done to enlarge the evaluated samples and looked possible mutations outside of the hot spot sequenced gene among discrepant strains.
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The sensitivities of spleen and lymph node cultures for the diagnosis of canine visceral leishmaniasis were compared in 64 anti-Leishmania antibody positive dogs from an endemic area in Brazil. The sensitivity of spleen cultures for Leishmania detection was 97.9%; in lymph node cultures it was 25%. Positive spleen culture was more frequent (p = 0.048, Fisher's exact probability test) in symptomatic (28 out of 33 animals) than in asymptomatic animals (19 out of 31 animals). These results support the use of spleen instead of lymph node aspiration as the choice method for the parasitological diagnosis of the infection.
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In occupational exposure assessment of airborne contaminants, exposure levels can either be estimated through repeated measurements of the pollutant concentration in air, expert judgment or through exposure models that use information on the conditions of exposure as input. In this report, we propose an empirical hierarchical Bayesian model to unify these approaches. Prior to any measurement, the hygienist conducts an assessment to generate prior distributions of exposure determinants. Monte-Carlo samples from these distributions feed two level-2 models: a physical, two-compartment model, and a non-parametric, neural network model trained with existing exposure data. The outputs of these two models are weighted according to the expert's assessment of their relevance to yield predictive distributions of the long-term geometric mean and geometric standard deviation of the worker's exposure profile (level-1 model). Bayesian inferences are then drawn iteratively from subsequent measurements of worker exposure. Any traditional decision strategy based on a comparison with occupational exposure limits (e.g. mean exposure, exceedance strategies) can then be applied. Data on 82 workers exposed to 18 contaminants in 14 companies were used to validate the model with cross-validation techniques. A user-friendly program running the model is available upon request.
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BACKGROUND: The early detection of medullary thyroid carcinoma (MTC) can improve patient prognosis, because histological stage and patient age at diagnosis are highly relevant prognostic factors. As a consequence, delay in the diagnosis and/or incomplete surgical treatment should correlate with a poorer prognosis for patients. Few papers have evaluated the specific capability of fine-needle aspiration cytology (FNAC) to detect MTC, and small series have been reported. This study conducts a meta-analysis of published data on the diagnostic performance of FNAC in MTC to provide more robust estimates. RESEARCH DESIGN AND METHODS: A comprehensive computer literature search of the PubMed/MEDLINE, Embase and Scopus databases was conducted by searching for the terms 'medullary thyroid' AND 'cytology', 'FNA', 'FNAB', 'FNAC', 'fine needle' or 'fine-needle'. The search was updated until 21 March 2014, and no language restrictions were used. RESULTS: Fifteen relevant studies and 641 MTC lesions that had undergone FNAC were included. The detection rate (DR) of FNAC in patients with MTC (diagnosed as 'MTC' or 'suspicious for MTC') on a per lesion-based analysis ranged from 12·5% to 88·2%, with a pooled estimate of 56·4% (95% CI: 52·6-60·1%). The included studies were statistically heterogeneous in their estimates of DR (I-square >50%). Egger's regression intercept for DR pooling was 0·03 (95% CI: -3·1 to 3·2, P = 0·9). The study that reported the largest MTC series had a DR of 45%. Data on immunohistochemistry for calcitonin in diagnosing MTC were inconsistent for the meta-analysis. CONCLUSIONS: The presented meta-analysis demonstrates that FNAC is able to detect approximately one-half of MTC lesions. These findings suggest that other techniques may be needed in combination with FNAC to diagnose MTC and avoid false negative results.
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This service Aims: To provide a multi-component weight management service that supports sustainable behaviour change and weight loss in adults 16 years and over with a BMI 28. To enable patients to develop the necessary personal attributes for their own long term weight management and to understand the impact of their weight on their health and co-morbidities. Objectives: To provide an evidence based, multi-component tier 2 weight management service that improves patients knowledge and skills for effective and sustainable weight loss helps patients identify their own facilitators for positive behaviour change and to address underlying barriers to long-term behaviour changeincreases patients self-efficacy and confidence in their ability to address their weight To be an integral part of the tiered approach to weight management services for the population of Stockton. To ensure equitable service provision across Stockton-on-Tees. To provide intensive group based service, one-to-one support and maintenance support. To support the service user to develop and review a personalised goal setting plan phase 2 and at discharge after phase 2. To ensure a smooth transition from the service (tier2) to tier 1 services to ensure continuity of care for service users.Recruit referrals using a variety of and appropriate methods. To establish a single point of contact for referrals into the service.Continually promote the service across a range of mediums and liaise and work in partnership with key interdependencies (refer to 2.4) To establish a robust database and data collection system in line with information governance. To ensure the access criteria, care pathway and referral process is clearly understood by all health care professionals and those who may refer into the service. To establish close links with, and signpost and/or enable service users to access suitable services where patient needs indicate this. This may include access to Tees Time to Talk (IAPT) for psychological therapies; Specialist Weight Management Service; physical activity programmes; Tier 1 services; and primary care. To provide the necessary venues, equipment and assets needed to deliver the programme, ensuring due regard is given to the quality and safety of all materials used. To collect and provide data in quarterly reports to the Commissioner to allow for continued monitoring and evaluation of the service in line with the Standard Evaluation Framework (available at www.noo.org.uk/core/SEF) and as specified by the Commissioner.
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Background: The imatinib trough plasma concentration (C(min)) correlates with clinical response in cancer patients. Therapeutic drug monitoring (TDM) of plasma C(min) is therefore suggested. In practice, however, blood sampling for TDM is often not performed at trough. The corresponding measurement is thus only remotely informative about C(min) exposure. Objectives: The objectives of this study were to improve the interpretation of randomly measured concentrations by using a Bayesian approach for the prediction of C(min), incorporating correlation between pharmacokinetic parameters, and to compare the predictive performance of this method with alternative approaches, by comparing predictions with actual measured trough levels, and with predictions obtained by a reference method, respectively. Methods: A Bayesian maximum a posteriori (MAP) estimation method accounting for correlation (MAP-ρ) between pharmacokinetic parameters was developed on the basis of a population pharmacokinetic model, which was validated on external data. Thirty-one paired random and trough levels, observed in gastrointestinal stromal tumour patients, were then used for the evaluation of the Bayesian MAP-ρ method: individual C(min) predictions, derived from single random observations, were compared with actual measured trough levels for assessment of predictive performance (accuracy and precision). The method was also compared with alternative approaches: classical Bayesian MAP estimation assuming uncorrelated pharmacokinetic parameters, linear extrapolation along the typical elimination constant of imatinib, and non-linear mixed-effects modelling (NONMEM) first-order conditional estimation (FOCE) with interaction. Predictions of all methods were finally compared with 'best-possible' predictions obtained by a reference method (NONMEM FOCE, using both random and trough observations for individual C(min) prediction). Results: The developed Bayesian MAP-ρ method accounting for correlation between pharmacokinetic parameters allowed non-biased prediction of imatinib C(min) with a precision of ±30.7%. This predictive performance was similar for the alternative methods that were applied. The range of relative prediction errors was, however, smallest for the Bayesian MAP-ρ method and largest for the linear extrapolation method. When compared with the reference method, predictive performance was comparable for all methods. The time interval between random and trough sampling did not influence the precision of Bayesian MAP-ρ predictions. Conclusion: Clinical interpretation of randomly measured imatinib plasma concentrations can be assisted by Bayesian TDM. Classical Bayesian MAP estimation can be applied even without consideration of the correlation between pharmacokinetic parameters. Individual C(min) predictions are expected to vary less through Bayesian TDM than linear extrapolation. Bayesian TDM could be developed in the future for other targeted anticancer drugs and for the prediction of other pharmacokinetic parameters that have been correlated with clinical outcomes.
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Coagulase-negative staphylococci (CNS) species identification is still difficult for most clinical laboratories. The scheme proposed by Kloos and Schleifer and modified by Bannerman is the reference method used for the identification of staphylococcal species and subspecies; however, this method is relatively laborious for routine use since it requires the utilization of a large number of biochemical tests. The objective of the present study was to compare four methods, i.e., the reference method, the API Staph system (bioMérieux) and two methods modified from the reference method in our laboratory (simplified method and disk method), in the identification of 100 CNS strains. Compared to the reference method, the simplified method and disk method correctly identified 100 and 99% of the CNS species, respectively, while this rate was 84% for the API Staph system. Inaccurate identification by the API Staph method was observed for Staphylococcus epidermidis (2.2%), S. hominis (25%), S. haemolyticus (37.5%), and S. warneri (47.1%). The simplified method using the simple identification scheme proposed in the present study was found to be efficient for all strains tested, with 100% sensitivity and specificity and proved to be available alternative for the identification of staphylococci, offering, higher reliability and lower cost than the currently available commercial systems. This method would be very useful in clinical microbiology laboratory, especially in places with limited resources.
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Since the 1990's, cheating athletes have abused substances to increase their oxygen transport capabilities; among these substances, recombinant EPO is the most well known. Currently, other investigational pharmaceutical products are able to produce an effect similar to EPO but without having chemical structures related to EPO; these are the synthetic erythropoiesis stimulating agents (ESAs). Peginesatide (also known as Hematide?) is being developed by Affymax and Takeda and, if approved by regulatory authorities, could soon be released on the international market. To detect potential athletic abuse of this product and deter athletes who consider cheating, we initiated a collaboration to implement a detection test for anti-doping purposes. Peginesatide is a synthetic, PEGylated, investigational, peptide-based erythropoiesis-stimulating agent that is designed and engineered to stimulate specifically the erythropoietin receptor dimer that governs erythropoiesis. It is undetectable using current anti-doping tests due to its lack of sequence homology to EPO. To detect and deter potential abuse of peginesatide, we initiated an industry/antidoping laboratory collaboration to develop and validate screening and confirmation assays so that they would be available before peginesatide reaches the market. We describe a screening ELISA and a confirmation assay consisting of immune-purification followed by separation with SDS-PAGE and revelation with Western double blotting. Both assays can detect 0.5 ng/mL concentrations of peginesatide in blood samples, enabling detection for several days after administration of a physiologically relevant dose. This initial report describes experimental characterization of these assays, including testing with a blinded set of samples from a clinical study conducted in healthy volunteers.