Validation, certification and registration of veterinary diagnostic test kits by the World Organisation for Animal Health Secretariat for Registration of Diagnostic Kits.

In the field of diagnostic test validation, World Organisation for Animal Health (OIE) Reference Laboratories (RLs) have a pivotal role and provide the international community with impartial advice and support in the selection, development and validation of diagnostic tests, which can be applied to the specialist diseases for which they are designated. National RLs provide an invaluable function in supporting the introduction, ongoing validation and application of validated diagnostic tests in line with international standards. Experienced staff with extensive knowledge of such systems and access to specialist facilities for conducting work are available to monitor changes or advancements in technology. They consider their relevance and value to evolving diagnostic test requirements. Reference Laboratories often have a broad mandate of activity linking research or development programmes and surveillance activities to benefit the continual assessment and, if necessary, improvement of diagnostic tools. Reference Laboratories maintain or have access to unique biological archives (known positive and negative sample populations) and produce international reference standards, both of which are vital in establishing the necessary and detailed validation of any diagnostic test. Reference Laboratories act either singularly or in collaborative partnerships with other RLs or science institutes, but also, when required, and with impartiality, with the commercial sector, to ensure new tests are validated according to OIE standards. They promote and apply formal programmes of quality assurance (including proficiency testing programmes) for newly validated tests, ensuring ongoing monitoring and compliance with standards, or as required set out any limitations or uncertainties. Reference Laboratories publish information on test validation in the scientific literature and on relevant websites, as well as disseminating information at workshops and international conferences. Furthermore, they can offer training in the processes and systems underpinning test validation.

Dans le domaine de la validation des tests de diagnostic, les Laboratoires de référence de l'Organisation mondiale de la santé animale (OIE) jouent un rôle central et fournissent à la communauté internationale des conseils impartiaux ainsi qu'un soutien pour la sélection, la mise au point et la validation des tests de diagnostic utilisés pour la détection des maladies correspondant à leur domaine de spécialisation. Les Laboratoires de référence nationaux remplissent une fonction inestimable en facilitant l'introduction, la validation continue et l'application de tests de diagnostic validés conformément aux normes internationales. Ces laboratoires sont dotés de personnels expérimentés possédant une connaissance approfondie de ces systèmes et qui ont accès à des installations spécialisées pour mener à bien leurs opérations et suivre de près les changements ou les avancées technologiques. Ils peuvent ainsi examiner leur pertinence et intérêt au regard de l'évolution des exigences relatives aux tests de diagnostic. Le mandat des Laboratoires de référence recouvre souvent un large éventail d'activités reliant les programmes de recherche ou développement et les activités de surveillance, ce qui permet de réaliser une évaluation continue des outils diagnostiques et, si besoin, de procéder à leur amélioration. Les Laboratoires de référence entretiennent ou ont accès à des banques de matériels biologiques uniques (panels d'échantillons positifs et négatifs connus) et produisent des réactifs de référence internationale, deux catégories de matériels essentielles pour procéder à la validation point par point d'un test diagnostique suivant les critères requis. Les Laboratoires de référence interviennent individuellement ou en partenariat avec d'autres Laboratoires de référence ou instituts scientifiques, mais aussi, lorsque c'est nécessaire et dans le respect des règles d'impartialité, avec le secteur privé, afin de s'assurer que les nouveaux tests sont validés conformément aux normes de l'OIE. Ils soutiennent et appliquent des programmes officiels d'assurance de la qualité (y compris en participant à des programmes d'essais d'aptitude inter-laboratoires) pour les tests nouvellement validés et garantissent leur suivi continu ainsi que leur conformité avec les normes, ou, suivant les cas, définissent les limites ou le niveau d'incertitude à prendre en considération. Les Laboratoires de référence publient les données relatives à la validation des tests dans des journaux scientifique et sur les sites Web pertinents et diffusent également des informations sur le sujet lors d'ateliers et de conférences internationales. En outre, ils peuvent proposer des formations sur les procédures et les systèmes qui sous-tendent la validation des tests.

En el terreno de la validación de pruebas de diagnóstico, los Laboratorios de Referencia de la Organización Mundial de Sanidad Animal (OIE) cumplen una función central y proporcionan a la comunidad internacional servicios de apoyo y asesoramiento imparcial para la selección, el desarrollo y la validación de pruebas de diagnóstico, que pueden aplicarse a la enfermedad para la que cada laboratorio esté designado. Los laboratorios de referencia nacionales cumplen una inestimable función de apoyo a la implantación, la continua validación y la utilización de pruebas de diagnóstico validadas con arreglo a las normas internacionales. Disponen de personal experimentado y muy buen conocedor de estos sistemas y de acceso a instalaciones especializadas de trabajo, lo que les permite seguir de cerca los cambios o adelantos tecnológicos y estudiar su utilidad o interés en relación con la evolución de los requisitos de las pruebas de diagnóstico. Los Laboratorios de Referencia suelen tener un mandato amplio, que a los programas de investigación y desarrollo aúna actividades de vigilancia, en aras de la continua evaluación y, en caso necesario, mejora de las herramientas de diagnóstico. Estos laboratorios poseen (o tienen acceso a) archivos biológicos únicos (conjuntos de muestras probadamente positivas y negativas) y elaboran patrones de referencia internacional, elementos ambos indispensables para llevar a buen fin la necesaria validación detallada de toda prueba de diagnóstico. Los Laboratorios de Referencia pueden trabajar en solitario o en colaboración con otros Laboratorios de Referencia, con institutos científicos e incluso, cuando hace falta, y procediendo con imparcialidad, con entidades del sector privado, a fin de garantizar que toda nueva prueba sea validada con arreglo a las normas de la OIE. También promueven y llevan adelante programas oficiales de garantía de la calidad de pruebas recién validadas (incluidos programas de pruebas de competencia), lo que asegura un seguimiento continuo y el cumplimiento de la normativa en todo momento, o fijan, cuando es necesario, limitaciones o niveles de incertidumbre. Asimismo, estos laboratorios publican datos sobre la validación de pruebas en revistas científicas y sitios web conexos y difunden información al respecto en talleres y conferencias internacionales. Además, pueden impartir formación sobre los procesos y sistemas que fundamentan la validación de pruebas de diagnóstico.

The experience of survival following allogeneic haematopoietic stem cell transplantation in New South Wales, Australia.

Allogeneic haematopoietic stem cell transplantation (allo-HSCT) entails long-term morbidities that impair survivors' quality of life through broad physical and psychosocial sequelae. Current data and survival measurements may be inadequate for contemporary Australian allo-HSCT recipients. This study sought to comprehensively describe survivorship in an up-to-date, local setting through validated measurements and a novel questionnaire designed to complement and address limitations of current instruments. All adults who received an allo-HSCT between 2000 and 2012 in New South Wales were eligible and included, if alive, those literate and consenting to the study, which encompassed seven survey instruments. Four hundred and forty-three survivors participated, which is 76% of contactable (n=583) and 66% of eligible survivors (n= 669). Chronic GVHD (cGVHD) and co-morbidity rates were similar to published data. Noteworthy results include prevalent sexual dysfunction (66% females, 52% males), loss of income (low income increased from 21 to 36%, P<0.001) and employment (full-time employment fell from 64 to 33%, P<0.001), suboptimal vaccination (31% complete), and health screening (≈50%). Risk factors for poor vaccination and health screening were cGVHD, younger age, less education, rural/regional residence and transplantation <2 years. This study suggests that improvement in survivorship may necessitate structural changes in the current delivery of health services.

Primary central nervous system posttransplantation lymphoproliferative disorder after heart and lung transplantation.

Primary central nervous system posttransplantation lymphoproliferative disorder (PCNS-PTLD) is uncommon, especially after heart or lung transplantation. Database analysis from a single heart and lung transplantation centre and a literature review pertaining to PCNS-PTLD was performed. In this study, the prevalence of PCNS-PTLD was 0.18% after heart and/or lung transplants. Of 1674 transplants, three cases of PCNS-PTLD developed 14 months, 9 years and 17 years posttransplant, and all were Epstein-Barr virus driven malignancies. Literature review of the topic revealed predominantly retrospective studies, with most reported cases after renal transplantation. The overall survival is poor, and it may be improved by early diagnosis and treatment. There are no published guidelines on the management of PCNS-PTLD; immune-chemotherapy in conjunction with reduction of immune suppression is preferred based on available evidence.

Health status, late effects and long-term survivorship of allogeneic bone marrow transplantation: a retrospective study.

BACKGROUND: Survival after allogeneic haemopoietic stem cell transplantation (allo-HSCT) has improved because of advancements in allo-HSCT. Allo-HSCT has been performed in Australia since the late 1970s. However, there are few published data about health problems of allo-HSCT survivors in Australia. AIMS: Identify health issues in long-term survivors of allo-HSCT in an Australian centre to manage better and prevent long-term complications. METHODS: The health records of all patients of allo-HSCT in a single centre from January 2000 to December 2007 and survived beyond 2 years were assessed. RESULTS: Ninety-nine of the 200 allo-HSCT patients survived beyond 2 years, and the median time from allo-HSCT was 74 months. Twenty-eight per cent died at a median of 37 months after allo-HSCT because of relapsed malignancy (12%), stroke (1%), infection (3%), chronic graft versus host disease (9%), secondary malignancy (2%) and unknown cause (1%). Ninety-one per cent reported one or more chronic health conditions. Health issues were chronic graft versus host disease (70%); respiratory (66%), ophthalmic (40%), bone (33%), and renal (26%) problems; and malignancies (14% skin, 3% solid organ). Seventy-nine per cent resumed vocation at full or reduced capacity 2 years after allo-HSCT. Clinicians identified 40% with quality of life (QOL) issues, but survivors' self-reported QOL was comparable with the general Australian population. CONCLUSION: This study shows that allo-HSCT patients are living with high burdens of chronic diseases that warrant lifelong surveillance and engagement with healthcare. Structured, multi-disciplinary care as recommended by published guidelines for allo-HSCT survivors may reduce long-term effects and improve their outcomes.

Diabetic ketoacidosis secondary to L-asparaginase in acute lymphoblastic leukaemia.

We describe a case of severe hyperglycaemia resulting in diabetic ketoacidosis secondary to L-asparaginase. There are few reports of this potentially life-threatening complication, particularly in the English literature. Awareness and recognition of this preventable and manageable problem will improve safe delivery of this anti-leukaemic drug.

Canadian regulatory requirements for recombinant fish vaccines.

In Canada, veterinary biological products derived by using conventional and new techniques of biotechnology are licensed and regulated under the Health of Animals Act and Regulations. Biological products include vaccines, bacterins, bacterin-toxoids and diagnostic kits which are used for the prevention, treatment or diagnosis of infectious diseases in all species of animals, including fish. Veterinary biologicals are licensed on the basis of fulfillment of four criteria: purity, potency, safety and efficacy. A risk-based approach is used to evaluate the safety of the product in target species, as well as non-target species, humans and the environment. On the basis of biological characteristics, biotechnology derived veterinary biologicals have been divided into two broad categories, high and low risk products. The paper describes the regulatory framework for the licensing of veterinary biologicals in Canada, with emphasis on the regulatory considerations for recombinant fish vaccines. Stages of movement of the product from research in a contained laboratory facility to a fully licensed product for free sale are discussed. The requirements for field testing and environmental assessment involved in these stages are highlighted. Manufacturers and researchers who intend to commercialize experimental vaccines are encouraged to consult with the Veterinary Biologics and Biotechnology Section early in the product development process so that the research data and quality assurance documentation are consistent with regulatory requirements.

The new Hawaii Comfort Care Only-Do Not Resuscitate law.

The new Hawaii law creating the Comfort Care Only-Do Not Resuscitate order allows terminally ill patients to be treated by ambulance personnel for comfort and pain control, and to not be resuscitated when they are near death.

The effects of scheduled intern rotation on the cost and quality of teaching hospital care.

We studied the effect of scheduled intern rotations on the cost and quality of inpatient care at one teaching hospital. For all discharges from the internal medicine service between 1980 and 1986, we identified 1,705 rotation patients and 3,141 no-rotation patients. Using linear or logistic regression analysis to control for baseline differences, we evaluated for the effect of rotation. We found that rotation was significantly related to longer length of hospital stay, b = 0.341 days, p = 0.001, and higher hospital charges (for log charges, b = 0.053, p = 0.016. Hospital deaths, nursing home placements, and 30-day readmissions were not significantly related to rotation, p > 0.1. These results suggest that the systematic discontinuity induced by scheduled intern rotations may be another source of increased health care costs experienced at teaching hospitals.

The effect of HMOs on premiums in employment-based health plans.

This study documents the effect of HMOs on premiums in employment-based health plans. We analyzed a survey of Minnesota employers conducted in 1986. Among 922 usable observations, 239 firms offered HMOs in addition to fee-for-service (FFS) health plans. We estimated an equation for the probability of offering an HMO, followed by equations for HMO enrollment share, and HMO and FFS premiums. The weighted average HMO and FFS premium in firms that offer HMOs was compared to the premium of FFS-only firms. We found that offering an HMO raises the average premium for family coverage health insurance by $25.14 per month and for single coverage by $3.68 per month. This effect was smaller for firms in the Twin Cities metropolitan area. HMOs may be viewed as a progressive and innovative health care benefit, but they are likely to increase firms' health insurance premiums.

A new intraoral flap: facial artery musculomucosal (FAMM) flap.

By combining the principles of nasolabial and buccal mucosal flaps, we have designed a new axial musculomucosal flap based on the facial artery. This flap has been designated the facial artery musculomucosal (FAMM) flap. The flap has proven to be reliable either superiorly based (retrograde flow) or inferiorly based (antegrade flow). It is versatile and has been used 18 times in 15 patients, with one failure and two partial losses. It has been used successfully to reconstruct a wide variety of difficult oronasal mucosal defects, including defects of the palate, alveolus, nasal septum, antrum, upper and lower lips, floor of the mouth, and soft palate.

Physician perspectives on the structure and function of group practice HMOs.

This article explores physicians' perspectives regarding how their HMOs function and their satisfaction with and loyalty to HMOs. Three HMOs were studied: a mature (28-year-old) staff model, a 16-year-old staff model, and a 13-year-old group model with both HMO and fee-for-service patients. While these HMOs were found to vary somewhat in terms of emphasis on patient care versus costs, methods used to control costs and degrees of centralization of decision making, they all received high overall satisfaction and loyalty scores. The staff model HMO with a more decentralized decision making structure received the highest satisfaction/loyalty score from its physicians. The degree to which physicians perceive the HMO to be effective and supportive and the use of educational programs and peer review to influence resource use were also found to be significantly related to physician satisfaction and loyalty.

A simultaneous equations model of employer strategies for controlling health benefit costs.

We estimated a simultaneous equations model of employer health insurance cost control strategies and their effectiveness in reducing health plan premiums. We hypothesized that as premiums increase, employers will shop more actively for health plans, place incentives on providers to control medical care costs, increase employee cost sharing for medical care, and be more likely to offer an HMO. In turn, we expected each of these strategies, except offering an HMO, to reduce average health plan premiums. The model was estimated with 1985 data from a sample of 922 Minnesota employers. We found that high premiums are related to three of the proposed cost control strategies. Employers with higher premiums shop more, are more likely to seek provider incentives, and offer an HMO. However, these employers appear to have lower employee cost sharing. Employers with higher employee cost sharing and those that offer an HMO had lower health plan premiums.

Epitope specificity of the protective immune response induced by individual bovine herpesvirus-1 glycoproteins.

Affinity-purified bovine herpesvirus-1 (BHV-1) glycoproteins gI, gIII and gIV, as well as a virus-free BHV-1-infected cell lysate were injected intramuscularly into seronegative calves. All immunized animals developed specific serum-neutralizing antibodies and they were fully protected from disease, using a BHV-1/Pasteurella haemolytica challenge model. After challenge, viral replication in the nasal passages was significantly reduced in animals vaccinated with gIV (10,000-fold) or BHV-1-infected cell lysate (450,000-fold) but just slightly reduced in animals immunized with gI (500-fold) or gIII (25-fold). All of the known epitopes of the glycoproteins were retained during the affinity-purification or preparation of the cell lysate. The high level of protection induced by gIV and the virus-infected cell lysate in particular indicates the potential of glycoprotein gIV as a subunit vaccine, ideally in combination with component(s) from the cell lysate, which may mediate cellular immune responses.

The relationship of house staff experience to the cost and quality of inpatient care.

The inexperience of house staff has been offered as one explanation for the increased cost of care at teaching hospitals, but conclusive evidence for this has been lacking. We studied the relationship of house staff experience to the cost and quality of inpatient care in a large series of internal medicine patients at one teaching hospital. We defined house staff experience by the month of academic year during which the patient received care. Our measures of cost were length of hospital stay and total hospital charges, while our measures of quality were hospital deaths, hospital readmissions, and nursing home placement. Multiple linear regression analysis on 21,679 hospital discharges revealed increasing house staff experience to be associated with a significant decline in length of stay (95% confidence interval for b, -0.006 to -0.066 days per discharge per month of house staff experience) and total hospital charges (95% confidence interval for b, -0.002 to -0.017 log dollars per discharge per month of house staff experience). These findings constitute an estimated average decline of 0.43 days per discharge and +370 per discharge over the academic year. Logistic regression analysis found no relationship of house staff experience to hospital deaths, readmissions, or nursing home placement. These findings suggest that the process of training inexperienced physicians may represent an important source of inefficiency for teaching hospitals struggling in a competitive environment.

Production of a factor (CIF) from normal fibroblast cells inhibiting tumor necrosis factor/cachectin production.

Murine embryonic fibroblast cells produce a factor designated cytotoxin-inhibiting factor (CIF) which inhibits tumor necrosis factor (TNF) and interleukin 1 production as well as tumoricidal activity by lipopolysaccharide-activated macrophages. This study determines the physiologic conditions of CIF production in serum-free medium. CIF production was largely dependent upon the presence of lipopolysaccharide. A quantitative correlation between fibroblast cell number, lipopolysaccharide concentration, and incubation time was established. Evidence is presented that CIF inhibited the production or release of TNF. CIF did not destroy TNF after production and release nor did it sequester secreted TNF. The supernatant fluids which inhibited TNF production did not suppress the capability of resting macrophages to phagocytize opsonized sheep erythrocytes, suggesting that only functions expressed in the activated state are inhibited.